Materiały źródłowe

• #1 Urinary Tract Infection: Pathogenesis and Outlook

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5159206/

  The clinical syndromes comprising urinary tract infection (UTI) continue to exert significant impact on millions of patients worldwide, most of whom are otherwise healthy women. […] Current therapeutics are suboptimal, as the prevalence of multidrug-resistant uropathogens is increasing and antibiotic treatment for acute infection does not preclude recurrences. […] The pathogenic cascade of UPEC cystitis has been extensively studied in recent years, largely in cell-culture and mouse models, as mice recapitulate many facets of the bladder epithelial environment. […] Through these studies, unprecedented light has been shed on the molecular and cellular basis of infection. […] Infection of the urinary tract begins when UPEC, likely introduced after colonization of the periurethral area by gastrointestinal tract flora, accesses and ascends the urethra by an undetermined mechanism.

• #2 Urinary tract infections: epidemiology, mechanisms of infection and treatment options

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4457377/

  Urinary tract infections (UTIs) are a severe public health problem and are caused by a range of pathogens, but most commonly by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterococcus faecalis and Staphylococcus saprophyticus. […] In this Review, we discuss how basic science studies are elucidating the molecular details of the crosstalk that occurs at the host-pathogen interface, as well as the consequences of these interactions for the pathophysiology of UTIs. […] Recent studies have used RNA sequencing to directly analyse uropathogens from the urine of women experiencing symptomatic UTIs. […] These studies have therefore revealed key virulence factors that can be targeted to prevent and counteract the pathogenic mechanisms that are important in UTIs. […] Adherence is a key event initiating each step in UTI pathogenesis.

• #3 Urinary Tract Infections: The Current Scenario and Future Prospects

  https://www.mdpi.com/2076-0817/12/4/623

  Urinary tract infections (UTIs) begin when gut-resident uropathogens colonize the urethra and subsequently the bladder through the action of specific adhesins. […] If the host’s inflammatory response fails to eliminate all bacteria, they begin to multiply, producing toxins and enzymes that promote their survival. […] Subsequent colonization of the kidneys can evolve into bacteremia if the pathogen crosses the kidney epithelial barrier. […] In complicated UTIs, infection by uropathogens is followed by bladder compromise, which occurs with catheterization. […] Uropathogens, through the expression of fibrinogen-binding proteins, bind to the catheter. […] Bacteria also multiply as a result of biofilm protection, and if the infection is left untreated, it can progress to pyelonephritis and bacteremia.

• #4 Host–pathogen interactions in urinary tract infection | Nature Reviews Urology

  https://www.nature.com/articles/nrurol.2010.101

  The urinary tract is a common site of bacterial infections; nearly half of all women experience at least one urinary tract infection (UTI) during their lifetime. […] Uropathogenic Escherichia coli and Proteus mirabilis are representative pathogens of uncomplicated and complicated urinary tract infection (UTI), respectively. […] Virulence and fitness factors synthesized by both pathogens include fimbriae, toxins, flagella, iron acquisition systems, and proteins that function in immune evasion. […] Additional factors that contribute to infection include the formation of intracellular bacterial communities by E. coli and the production of urease by P. mirabilis, which can result in urinary stone formation. […] Innate immune responses are induced or mediated by pattern recognition receptors, antimicrobial peptides, and neutrophils; the adaptive immune response to UTI is less well understood.

• #5 Urinary tract infections: epidemiology, mechanisms of infection and treatment options

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4457377/

  Urinary tract infections (UTIs) are a severe public health problem and are caused by a range of pathogens, but most commonly by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterococcus faecalis and Staphylococcus saprophyticus. […] In this Review, we discuss how basic science studies are elucidating the molecular details of the crosstalk that occurs at the host-pathogen interface, as well as the consequences of these interactions for the pathophysiology of UTIs. […] Recent studies have used RNA sequencing to directly analyse uropathogens from the urine of women experiencing symptomatic UTIs. […] These studies have therefore revealed key virulence factors that can be targeted to prevent and counteract the pathogenic mechanisms that are important in UTIs. […] Adherence is a key event initiating each step in UTI pathogenesis.

• #6 Urinary Tract Infections: The Current Scenario and Future Prospects

  https://www.mdpi.com/2076-0817/12/4/623

  Most UTIs are caused by Gram-negative and Gram-positive bacteria residing in the colon, such as Escherichia coli, Enterococcus faecalis, Proteus mirabilis, and Klebsiella pneumoniae. […] These uropathogens use different types of adhesins that promote binding and biofilm formation on biotic and abiotic surfaces. […] Biofilm formation by these pathogenic bacteria requires specific virulence factors that play a key role in inducing adhesion to host epithelial cells or catheter materials. […] Bacterial biofilms play an important role in UTIs, being responsible for the persistence of infections that result in recurrence and relapse. […] The main virulence factors involved in host cell adhesion are Type 1 and Type 2 fimbriae, P fimbriae, Dr adhesion, S fimbriae, and F1C fimbriae. […] UPEC strains express a broad spectrum of virulence factors, but their ability to cause UTIs is fundamentally related to their ability to produce a number of adhesins that can facilitate adhesion under different environmental conditions.

• #7 Urinary tract infections: epidemiology, mechanisms of infection and treatment options | Nature Reviews Microbiology

  https://www.nature.com/articles/nrmicro3432

  Urinary tract infections (UTIs) are some of the most common bacterial infections and are caused by both Gram-negative and Gram-positive species. UTIs are categorized into uncomplicated and complicated, and are a severe public health problem; this situation is being exacerbated by the rise in multidrug-resistant strains. […] Uropathogens carry multiple virulence factors involved in the pathophysiology of UTIs. These virulence factors are involved in invasion and colonization, as well as in mediating the subversion of host defences. […] Knowledge about the mechanism of action of these virulence factors is being used to develop new therapeutics against UTIs. […] Therapies that are currently in the initial stages of development include vaccines targeting bacterial factors that are essential for initial attachment and disease progression (such as adhesins, toxins, proteases and siderophores), and small-molecule inhibitors that prevent adhesin-receptor interactions. […] In this Review, we discuss how basic science studies are elucidating the molecular details of the crosstalk that occurs at the host-pathogen interface, as well as the consequences of these interactions for the pathophysiology of UTIs.

• #8 Urinary Tract Infection, UTI – Pathogenesis, Route of Infection

  https://studymicrobio.com/urinary-tract-infection-uti-pathogenesis-route-of-infection/

  Bacteria can invade and cause a Urinary Tract Infection (UTI) via 3 major routes: […] It is the most common course of infection in females. But mostly it is associated with instrumentation (eg. urinary catheterization, cystoscopy) and is the most common cause of hospital-acquired Urinary Tract Infection (UTI) in both sexes. […] For Urinary Tract Infection (UTI) to occur by the ascending pathway, enteric gram-negative bacteria and other microorganisms that originate in the Gastro-Intestinal (GI) tract must be able to colonize the vaginal cavity or the periurethral area. […] Once these organisms gain access to the bladder, they may multiply and then pass up to the ureters to the kidneys. Both sexual activity and anatomical design (short urethra and its proximity to anus) in females contribute to increased causes of Urinary Tract Infection (UTI).

• #9 Urinary Tract Infection (UTI) and Cystitis (Bladder Infection) in Females: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/233101-overview

  Frequent and complete voiding has been associated with a reduction in the incidence of UTI. Normally, a thin film of urine remains in the bladder after emptying, and any bacteria present are removed by the mucosal cell production of organic acids. […] If the defense mechanisms of the lower urinary tract fail, upper tract or kidney involvement occurs and is termed pyelonephritis. Host defenses at this level include local leukocyte phagocytosis and renal production of antibodies that kill bacteria in the presence of complement. […] In general, there are 3 main mechanisms responsible for UTIs: colonization with ascending spread, hematogenous spread, periurogenital spread. […] Uropathogenic bacteria, derived from a subset of fecal flora, have traits that enable adherence, growth, and resistance of host defenses. These traits facilitate colonization and infection of the urinary tract.

• #10 Causes, Pathogens, and Risk Faktors of Urinary Tract Infection

  https://www.urology-textbook.com/urinary-tract-infection-causes.html

  Bacteria can invade the urinary tract by ascending from the urethra, hematogenous spread, lymphatic spread and invasion via the neighboring organs. […] Ascending infections are the most common cause of urinary tract infections. Because the female urethra is short and intestinal bacteria tend to colonize the perineum and vulva, women are more prone to UTIs than men. […] Hematogenous-caused urinary tract infections are rare: urogenital tuberculosis, renal abscess, perinephric abscess, or epididymitis. […] Lymphatic causes of UTI are rare and speculative; bacteria may spread to the prostate, bladder, and female internal genital organs in case of severe bowel inflammation. […] Urinary tract infections may be causes by invasion from neighboring organs: through intraperitoneal abscess, pelvic inflammatory disease, bowel fistula (Crohn disease, diverticulitis, cancer), vesicovaginal fistula.

• #11 Overview of Urinary Tract Infections (UTIs) – Kidney and Urinary Tract Disorders – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/kidney-and-urinary-tract-disorders/urinary-tract-infections-utis/overview-of-urinary-tract-infections-utis

  In healthy people, urine in the bladder is sterile—no bacteria or other infectious organisms are present. However, any part of the urinary tract can become infected. An infection anywhere along the urinary tract is called a urinary tract infection (UTI). […] The organisms that cause infection usually enter the urinary tract by one of two routes. The most common route by far is through the lower end of the urinary tract—the opening of a man’s urethra at the tip of the penis or the opening of a woman’s urethra at the vulva. The infection ascends the urethra to the bladder, and sometimes to the kidneys, or both. The other possible route is through the bloodstream, usually to the kidneys. […] Urinary tract infections (UTIs) are almost always caused by bacteria, although some viruses, fungi, and parasites can infect the urinary tract as well. More than 85% of UTIs are caused by bacteria from the intestine or vagina. Ordinarily, however, bacteria that enter the urinary tract are washed out by the flushing action of the bladder as it empties.

• #12 Urinary Tract Infection, UTI – Pathogenesis, Route of Infection

  https://studymicrobio.com/urinary-tract-infection-uti-pathogenesis-route-of-infection/

  The presence of yeast (usually Candida albicans), Mycobacterium tuberculosis, Salmonella spp., Leptospira spp., or S. aureus in the urine often indicates pyelonephritis acquired via hematogenous spread or the descending route. Hematogenous spread accounts for 5% of Urinary Tract infections (UTI). […] Urinary Tract Infection (UTI) through this pathway may be the result of increased pressure on the bladder that causes the lymphatic flow to the kidneys.

• #13 Bacterial Urinary Tract Infections – Genitourinary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/genitourinary-disorders/urinary-tract-infections-utis/bacterial-urinary-tract-infections

  In 95% of cases of pyelonephritis, the cause is ascension of bacteria through the urinary tract. Although obstruction predisposes to pyelonephritis, most women with pyelonephritis have no demonstrable functional or anatomic defects. In men, pyelonephritis is always due to some functional or anatomic defect. Cystitis alone or anatomic defects may cause reflux. The risk of bacterial ascension is greatly enhanced when ureteral peristalsis is inhibited. […] Pyelonephritis not caused by bacterial ascension is caused by hematogenous spread, which is particularly characteristic of virulent organisms such as S. aureus, P. aeruginosa, Salmonella species, and Candida species. […] The affected kidney is usually enlarged because of inflammatory polymorphonuclear neutrophils and edema. Infection is focal and patchy, beginning in the pelvis and medulla and extending into the cortex as an enlarging wedge. Cells mediating chronic inflammation appear within a few days, and medullary and subcortical abscesses may develop. Normal parenchymal tissue between foci of infection is common. […] Papillary necrosis may occur in acute pyelonephritis associated with diabetes, obstruction, sickle cell disease, pyelonephritis in renal transplants, pyelonephritis due to candidiasis, or analgesic nephropathy.

• #14 Urinary Tract Infection, UTI – Pathogenesis, Route of Infection

  https://studymicrobio.com/urinary-tract-infection-uti-pathogenesis-route-of-infection/

  The presence of yeast (usually Candida albicans), Mycobacterium tuberculosis, Salmonella spp., Leptospira spp., or S. aureus in the urine often indicates pyelonephritis acquired via hematogenous spread or the descending route. Hematogenous spread accounts for 5% of Urinary Tract infections (UTI). […] Urinary Tract Infection (UTI) through this pathway may be the result of increased pressure on the bladder that causes the lymphatic flow to the kidneys.

• #15 Urinary Tract Infections Caused by Uropathogenic Escherichia coli: Mechanisms of Infection and Treatment Options

  https://www.mdpi.com/1422-0067/24/13/10537

  The urethra has a self-defense function and usually prevents UTIs. The urethral mucosa and epithelial cells can resist the invasion of pathogenic bacteria, maintaining a balance between the urethra and bacteria. However, when the pathogenicity of bacteria is very strong, or the body suffers from external damage, this balance is disturbed, and the defense function of the body is compromised. Subsequently, a series of inflammatory reactions occur in the urinary tract, such as urethritis, cystitis, and pyelonephritis. Certain factors of UPEC often play an important role in these reactions, such as lipopolysaccharides (LPSs), polysaccharide capsules, flagella, outer-membrane vesicles, fimbriae, curli, non-fimbrial adhesins, outer-membrane proteins (OMPs), and iron-acquisition receptors. […] The first step is UPEC-induced periurethral and vaginal invasion and colonization. Various fimbriae and adhesins on the surface of UPEC play a pivotal role in mediating adhesion and colonization. The second step is ascension into the bladder lumen and growth as planktonic cells in the urine. The third step is adherence to the surface and interaction with the defensive system of the bladder epithelium. The fourth step is biofilm formation. UPEC proliferate and accumulate to a certain degree to form the biofilm. The biofilm is important in ensuring that bacterial pathogens can colonize the urinary tract and cause infection. Once the biofilm is formed, it may elude immune defense mechanisms. At the same time, the biofilm also exhibits strong drug resistance, and it is difficult for drugs to penetrate the biofilm, leading to chronic and recurrent UTIs.

• #16 Urinary Tract Infections Caused by Uropathogenic Escherichia coli: Mechanisms of Infection and Treatment Options

  https://www.mdpi.com/1422-0067/24/13/10537

  The urethra has a self-defense function and usually prevents UTIs. The urethral mucosa and epithelial cells can resist the invasion of pathogenic bacteria, maintaining a balance between the urethra and bacteria. However, when the pathogenicity of bacteria is very strong, or the body suffers from external damage, this balance is disturbed, and the defense function of the body is compromised. Subsequently, a series of inflammatory reactions occur in the urinary tract, such as urethritis, cystitis, and pyelonephritis. Certain factors of UPEC often play an important role in these reactions, such as lipopolysaccharides (LPSs), polysaccharide capsules, flagella, outer-membrane vesicles, fimbriae, curli, non-fimbrial adhesins, outer-membrane proteins (OMPs), and iron-acquisition receptors. […] The first step is UPEC-induced periurethral and vaginal invasion and colonization. Various fimbriae and adhesins on the surface of UPEC play a pivotal role in mediating adhesion and colonization. The second step is ascension into the bladder lumen and growth as planktonic cells in the urine. The third step is adherence to the surface and interaction with the defensive system of the bladder epithelium. The fourth step is biofilm formation. UPEC proliferate and accumulate to a certain degree to form the biofilm. The biofilm is important in ensuring that bacterial pathogens can colonize the urinary tract and cause infection. Once the biofilm is formed, it may elude immune defense mechanisms. At the same time, the biofilm also exhibits strong drug resistance, and it is difficult for drugs to penetrate the biofilm, leading to chronic and recurrent UTIs.

• #17 Urinary Tract Infections Caused by Uropathogenic Escherichia coli: Mechanisms of Infection and Treatment Options

  https://www.mdpi.com/1422-0067/24/13/10537

  The urethra has a self-defense function and usually prevents UTIs. The urethral mucosa and epithelial cells can resist the invasion of pathogenic bacteria, maintaining a balance between the urethra and bacteria. However, when the pathogenicity of bacteria is very strong, or the body suffers from external damage, this balance is disturbed, and the defense function of the body is compromised. Subsequently, a series of inflammatory reactions occur in the urinary tract, such as urethritis, cystitis, and pyelonephritis. Certain factors of UPEC often play an important role in these reactions, such as lipopolysaccharides (LPSs), polysaccharide capsules, flagella, outer-membrane vesicles, fimbriae, curli, non-fimbrial adhesins, outer-membrane proteins (OMPs), and iron-acquisition receptors. […] The first step is UPEC-induced periurethral and vaginal invasion and colonization. Various fimbriae and adhesins on the surface of UPEC play a pivotal role in mediating adhesion and colonization. The second step is ascension into the bladder lumen and growth as planktonic cells in the urine. The third step is adherence to the surface and interaction with the defensive system of the bladder epithelium. The fourth step is biofilm formation. UPEC proliferate and accumulate to a certain degree to form the biofilm. The biofilm is important in ensuring that bacterial pathogens can colonize the urinary tract and cause infection. Once the biofilm is formed, it may elude immune defense mechanisms. At the same time, the biofilm also exhibits strong drug resistance, and it is difficult for drugs to penetrate the biofilm, leading to chronic and recurrent UTIs.

• #18 Urinary Tract Infection: Pathogenesis and Outlook

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5159206/

  Upon reaching the urinary bladder, UPEC bind to superficial epithelial (facet) cells in a type 1 pili-dependent manner. […] A subset of adherent bacteria are then internalized into facet cells, a dynamic process that likely relies on the normal cycling of apical membrane segments in these cells. […] Recent data show that UPEC are capable of neutralizing the lysosome, and that this neutralization is sensed by a lysosomal membrane protein termed mucolipin TRP channel 3 (TRPML3), activating pathways that direct exocytosis of UPEC-containing lysosomes. […] Using incompletely defined strategies, UPEC may gain access to the bladder epithelial cell cytoplasm, thereafter developing clonal, biofilm-like masses termed intracellular bacterial communities (IBCs). […] After 16-24 h in murine UTI models, a subset of UPEC in remaining IBCs adopt a neutrophil-resistant, filamentous morphology and escape the IBCs, subsequently re-invading nave bladder epithelial cells.

• #19 Urinary tract infections: epidemiology, mechanisms of infection and treatment options

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4457377/

  A UTI typically starts with periurethral contamination by a uropathogen residing in the gut, followed by colonization of the urethra and subsequent migration of the pathogen to the bladder, an event that requires appendages such as flagella and pili. […] Multiple bacterial adhesins recognize receptors on the bladder epithelium and mediate colonization. […] Uropathogens such as UPEC survive by invading the bladder epithelium, producing toxins and proteases to release nutrients from the host cells, and synthesizing siderophores to obtain iron. […] Consequently, the uropathogens are able to cross the tubular epithelial barrier to access the blood stream, initiating bacteraemia. […] The uropathogens that cause uncomplicated UTIs, including UPEC, K. pneumoniae and S. saprophyticus, have the ability to bind directly to the bladder epithelium.

• #20 Urinary Tract Infection: Pathogenesis and Outlook

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5159206/

  Upon reaching the urinary bladder, UPEC bind to superficial epithelial (facet) cells in a type 1 pili-dependent manner. […] A subset of adherent bacteria are then internalized into facet cells, a dynamic process that likely relies on the normal cycling of apical membrane segments in these cells. […] Recent data show that UPEC are capable of neutralizing the lysosome, and that this neutralization is sensed by a lysosomal membrane protein termed mucolipin TRP channel 3 (TRPML3), activating pathways that direct exocytosis of UPEC-containing lysosomes. […] Using incompletely defined strategies, UPEC may gain access to the bladder epithelial cell cytoplasm, thereafter developing clonal, biofilm-like masses termed intracellular bacterial communities (IBCs). […] After 16-24 h in murine UTI models, a subset of UPEC in remaining IBCs adopt a neutrophil-resistant, filamentous morphology and escape the IBCs, subsequently re-invading nave bladder epithelial cells.

• #21 Urinary Tract Infection: Pathogenesis and Outlook

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5159206/

  Upon reaching the urinary bladder, UPEC bind to superficial epithelial (facet) cells in a type 1 pili-dependent manner. […] A subset of adherent bacteria are then internalized into facet cells, a dynamic process that likely relies on the normal cycling of apical membrane segments in these cells. […] Recent data show that UPEC are capable of neutralizing the lysosome, and that this neutralization is sensed by a lysosomal membrane protein termed mucolipin TRP channel 3 (TRPML3), activating pathways that direct exocytosis of UPEC-containing lysosomes. […] Using incompletely defined strategies, UPEC may gain access to the bladder epithelial cell cytoplasm, thereafter developing clonal, biofilm-like masses termed intracellular bacterial communities (IBCs). […] After 16-24 h in murine UTI models, a subset of UPEC in remaining IBCs adopt a neutrophil-resistant, filamentous morphology and escape the IBCs, subsequently re-invading nave bladder epithelial cells.

• #22 Urinary Tract Infections Caused by Uropathogenic Escherichia coli: Mechanisms of Infection and Treatment Options

  https://www.mdpi.com/1422-0067/24/13/10537

  The fifth step is invasion and replication via the formation of IBCs in the bladder, where quiescent intracellular reservoirs (QIRs) arise in the underlying urothelium. Bacterial replication in these IBCs can easily reach as high as 10^5 bacteria per cell. Additionally, bacteria in the IBCs undergo morphological changes, emerge from the infected cell, and enter neighboring cells, which spreads the infection. The sixth step is kidney colonization. UPEC destroy host tissues by releasing toxins, causing upper UTIs, and severe cases may lead to dangerous conditions, including bacteremia, septicemia, urosepsis, and even death. […] In general, the strategies of pathogenesis employed by UPEC include adherence, motility, the acquisition of metals, toxin production, and immune evasion. The bacterial adhesins and their receptors on the host’s cells mediate the processes of bacterial colonization, biofilm formation, replication, secretion of toxins, internalization, and invasion.

• #23 Urinary Tract Infection: Pathogenesis and Outlook

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5159206/

  Upon reaching the urinary bladder, UPEC bind to superficial epithelial (facet) cells in a type 1 pili-dependent manner. […] A subset of adherent bacteria are then internalized into facet cells, a dynamic process that likely relies on the normal cycling of apical membrane segments in these cells. […] Recent data show that UPEC are capable of neutralizing the lysosome, and that this neutralization is sensed by a lysosomal membrane protein termed mucolipin TRP channel 3 (TRPML3), activating pathways that direct exocytosis of UPEC-containing lysosomes. […] Using incompletely defined strategies, UPEC may gain access to the bladder epithelial cell cytoplasm, thereafter developing clonal, biofilm-like masses termed intracellular bacterial communities (IBCs). […] After 16-24 h in murine UTI models, a subset of UPEC in remaining IBCs adopt a neutrophil-resistant, filamentous morphology and escape the IBCs, subsequently re-invading nave bladder epithelial cells.

• #24 Urinary Tract Infection: Pathogenesis and Outlook

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5159206/

  Some of these bacteria will go on to infect immature bladder epithelium which is exposed after exfoliation, later forming quiescent intracellular reservoirs, which avoid immune clearance and resist systemic antibiotic treatment. […] These persistent UPEC may re-emerge, in response to currently undefined signals, to cause the recurrent cystitis that is so clinically common. […] A significant gap in our understanding is the mechanism by which UPEC escape the initial vacuole (after internalization) to reach the cytoplasm, where the IBC is formed. […] Following escape into the cytoplasm, the bacteria find themselves occupying an environment very different from the nutrient-poor bladder lumen. […] Transcriptomic analyses of UPEC in different models have suggested that various metabolic pathways are essential for pathogenesis; these include sialic acid transport/metabolism, gluconeogenesis, the tricarboxylic acid (TCA) cycle, iron uptake, ethanolamine and phosphate metabolism, as well as amino acid metabolism.

• #25 Urinary Tract Infections Caused by Uropathogenic Escherichia coli: Mechanisms of Infection and Treatment Options

  https://www.mdpi.com/1422-0067/24/13/10537

  The fifth step is invasion and replication via the formation of IBCs in the bladder, where quiescent intracellular reservoirs (QIRs) arise in the underlying urothelium. Bacterial replication in these IBCs can easily reach as high as 10^5 bacteria per cell. Additionally, bacteria in the IBCs undergo morphological changes, emerge from the infected cell, and enter neighboring cells, which spreads the infection. The sixth step is kidney colonization. UPEC destroy host tissues by releasing toxins, causing upper UTIs, and severe cases may lead to dangerous conditions, including bacteremia, septicemia, urosepsis, and even death. […] In general, the strategies of pathogenesis employed by UPEC include adherence, motility, the acquisition of metals, toxin production, and immune evasion. The bacterial adhesins and their receptors on the host’s cells mediate the processes of bacterial colonization, biofilm formation, replication, secretion of toxins, internalization, and invasion.

• #26 Urinary Tract Infections: The Current Scenario and Future Prospects

  https://www.mdpi.com/2076-0817/12/4/623

  Urinary tract infections (UTIs) begin when gut-resident uropathogens colonize the urethra and subsequently the bladder through the action of specific adhesins. […] If the host’s inflammatory response fails to eliminate all bacteria, they begin to multiply, producing toxins and enzymes that promote their survival. […] Subsequent colonization of the kidneys can evolve into bacteremia if the pathogen crosses the kidney epithelial barrier. […] In complicated UTIs, infection by uropathogens is followed by bladder compromise, which occurs with catheterization. […] Uropathogens, through the expression of fibrinogen-binding proteins, bind to the catheter. […] Bacteria also multiply as a result of biofilm protection, and if the infection is left untreated, it can progress to pyelonephritis and bacteremia.

• #27 Urinary Tract Infections Caused by Uropathogenic Escherichia coli: Mechanisms of Infection and Treatment Options

  https://www.mdpi.com/1422-0067/24/13/10537

  The fifth step is invasion and replication via the formation of IBCs in the bladder, where quiescent intracellular reservoirs (QIRs) arise in the underlying urothelium. Bacterial replication in these IBCs can easily reach as high as 10^5 bacteria per cell. Additionally, bacteria in the IBCs undergo morphological changes, emerge from the infected cell, and enter neighboring cells, which spreads the infection. The sixth step is kidney colonization. UPEC destroy host tissues by releasing toxins, causing upper UTIs, and severe cases may lead to dangerous conditions, including bacteremia, septicemia, urosepsis, and even death. […] In general, the strategies of pathogenesis employed by UPEC include adherence, motility, the acquisition of metals, toxin production, and immune evasion. The bacterial adhesins and their receptors on the host’s cells mediate the processes of bacterial colonization, biofilm formation, replication, secretion of toxins, internalization, and invasion.

• #28 The Pathogenesis of Urinary Tract Infections | IntechOpen

  https://www.intechopen.com/chapters/19318

  An understanding of pathogenic and anti-adherence mechanisms may allow physicians to develop appropriate strategies for UTI prevention and adequate management protocols. In the present chapter we discuss current concepts on the pathogenesis of UTIs with particular emphasis on pathogenic bacteria, virulence factors, predisposing factors, natural defences within genitourinary tract and consequences when these defence mechanisms are altered. […] Bacterial virulence factors play a significant role in determining whether an organism will invade the urinary tract and the level of infection acquired. Uropathogenic E. coli (UPEC) is present within bowel flora and pathogenic strains of this microorganism can infect the urinary tract by expressing specific virulence factors that permit adherence and colonisation of the lower urinary tract (Schlager et al. 2002, Yamamoto et al. 1997). Adherence of the micro-organism is dependent on 3 important environmental characteristics; firstly the bacterias own adhesive characteristics, secondly the receptive features of the urothelium and finally the fluid that is present between both surfaces (Schaeffer et al. 1981). Bacteria will migrate proximally and precipitate a host derived inflammatory response after adhering to the mucosal surface.

• #29 The Pathogenesis of Urinary Tract Infections | IntechOpen

  https://www.intechopen.com/chapters/19318

  Adhesins found on the surface of the bacterial membrane are responsible for initial attachment onto urinary tract tissues (Mulvey 2002). […] Adhesins are classified as fimbrial or afimbrial, depending on whether the adhesin is displayed as part of a rigid fimbria or pilus. Fimbriae and pili are surface glycoproteins that function as ligands for glycolipid and glycoprotein receptors on uroepithelial cells. […] After binding to the epithelial surface the activated Fim H adhesins migrate towards deeper urothelial layers and penetrate the cell membrane (Mulvey et al. 2000). Once the uropathogen is intracellular the invasive process continues as bacteria proliferate within the cytosol to form clusters (Anderson et al. 2004b). […] The hosts innate immune response is primarily responsible for providing resistance to the invading uropathogen. Numerous cell types such as neutrophils, macrophages, eosinophils and natural killer cells are activated as the uropathogen invades.

• #30 Role of D-mannose in urinary tract infections – a narrative review | Nutrition Journal | Full Text

  https://nutritionj.biomedcentral.com/articles/10.1186/s12937-022-00769-x

  Urinary tract infections (UTIs) are one of the most prevalent bacterial diseases worldwide. […] D-mannose, a monosaccharide naturally found in fruits, is commonly marketed as a dietary supplement for reducing the risk for UTIs. […] When excreted in urine, D-mannose potentially inhibits Escherichia coli, the main causative organism of UTIs, from attaching to urothelium and causing infection. […] The adhesion of E. coli in the urinary tract is mainly based on mannose-sensitive mechanism, where E. coli type I pili adhere to mannose structures on the uroepithelial cell surfaces. […] Research suggests that free D-mannose in urine has the potential to saturate E. coli FimH structures, and subsequently block E. coli adhesion to urinary tract epithelial cells. This so-called competitive inhibition is considered as one of the potential mechanisms for preventing UTI development.

• #31 Role of D-mannose in urinary tract infections – a narrative review | Nutrition Journal | Full Text

  https://nutritionj.biomedcentral.com/articles/10.1186/s12937-022-00769-x

  The pathogenicity of UTI associated bacteria is based on their ability to attach, colonize, and survive in the urinary tract environment. UPEC strains possess several virulence factors, such as adhesins, toxins, iron acquisition factors, lipopolysaccharide and capsules, that contribute to UTI pathogenesis. One of the main disease-causing mechanisms for UPEC is based on its adherence to mannosylated protein components called uroplakins on the bladder epithelium. […] The attachment activates signal cascades causing actin rearrangement, which ultimately leads to an internalization of the bacteria into the umbrella cells of the epithelium. […] UPEC strains employ several strategies to evade the host immune system, which facilitates formation of intracellular bacterial communities (IBCs); this enables bacteria to multiply, mature and infect other cells.

• #32 Urinary Tract Infections Caused by Uropathogenic Escherichia coli: Mechanisms of Infection and Treatment Options

  https://www.mdpi.com/1422-0067/24/13/10537

  The role of P fimbriae in UTIs is complex and has not yet been fully explored, but a substantial amount of evidence demonstrates its importance to UPEC. […] The number of papIBAHCDJKEFG—10 kbp operons located on pathogenicity islands (PAIs)—depends on various classes of adhesin subunits (ranging from 9 to 12 genes). […] The primary function of siderophores, which are small chelating molecules with a very high affinity for iron, is assumed to be scavenging ferric iron (Fe3+). […] In short, nearly all common iron-acquisition-associated genes are significantly positively selected in UPEC clinical isolates. […] The IBC pathway is a significant target for therapeutic intervention. […] The infection causes the host to have a significant pro-inflammatory reaction, which is followed by an inflow of neutrophils and attempted eradication of bacteria.

• #33 Urinary Tract Infections: The Current Scenario and Future Prospects

  https://www.mdpi.com/2076-0817/12/4/623

  Most UTIs are caused by Gram-negative and Gram-positive bacteria residing in the colon, such as Escherichia coli, Enterococcus faecalis, Proteus mirabilis, and Klebsiella pneumoniae. […] These uropathogens use different types of adhesins that promote binding and biofilm formation on biotic and abiotic surfaces. […] Biofilm formation by these pathogenic bacteria requires specific virulence factors that play a key role in inducing adhesion to host epithelial cells or catheter materials. […] Bacterial biofilms play an important role in UTIs, being responsible for the persistence of infections that result in recurrence and relapse. […] The main virulence factors involved in host cell adhesion are Type 1 and Type 2 fimbriae, P fimbriae, Dr adhesion, S fimbriae, and F1C fimbriae. […] UPEC strains express a broad spectrum of virulence factors, but their ability to cause UTIs is fundamentally related to their ability to produce a number of adhesins that can facilitate adhesion under different environmental conditions.

• #34 Urinary Tract Infection (UTI) and Cystitis (Bladder Infection) in Females: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/233101-overview

  Adhesins are bacterial surface structures that enable attachment to host membranes. In E coli infection, these include both pili (ie, fimbriae) and outer-membrane proteins (eg, Dr hemagglutinin that binds to Dr blood group antigen). P fimbriae, which attach to globoseries-type glycolipids found in the colon and urinary epithelium, are associated with pyelonephritis and cystitis and are found in many E coli strains that cause urosepsis. […] Most uropathogens gain access to the urinary tract via an ascending route. The shorter length of the female urethra allows uropathogens easier access to the bladder. The continuous unidirectional flow of urine helps to minimize UTIs, and anything that interferes with this increases the host’s susceptibility to UTI. Examples of interference include volume depletion, sexual intercourse, urinary tract obstruction, instrumentation, use of catheters not drained to gravity, and vesicoureteral reflux.

• #35 Pathogenesis of Urinary Tract Infections | Encyclopedia MDPI

  https://encyclopedia.pub/entry/45913

  Uropathogenic E. coli (UPEC) is the most common causative agent of both uUTIs and cUTIs. […] On the cell surface of uropathogens are several adhesion proteins that play a crucial role in the initial interactions between the host and pathogen. […] In addition, adhesins have recently been found to promote both the attachment of bacteria and invasion of host tissues in the urinary tract. […] Biofilm formation by these pathogenic bacteria requires specific virulence factors that play a key role in inducing adhesion to host epithelial cells or catheter materials. […] Bacterial biofilms play an important role in UTIs, being responsible for the persistence of infections that result in recurrence and relapse. […] Since eradication of biofilms often cannot be achieved by antibiotic treatment, new approaches for eradication of aggressive biofilms are being tested, such as phagotherapy, enzymatic degradation, antimicrobic peptides, and nanoparticles.

• #36 Urinary tract infections: epidemiology, mechanisms of infection and treatment options | Nature Reviews Microbiology

  https://www.nature.com/articles/nrmicro3432

  Urinary tract infections (UTIs) are some of the most common bacterial infections and are caused by both Gram-negative and Gram-positive species. UTIs are categorized into uncomplicated and complicated, and are a severe public health problem; this situation is being exacerbated by the rise in multidrug-resistant strains. […] Uropathogens carry multiple virulence factors involved in the pathophysiology of UTIs. These virulence factors are involved in invasion and colonization, as well as in mediating the subversion of host defences. […] Knowledge about the mechanism of action of these virulence factors is being used to develop new therapeutics against UTIs. […] Therapies that are currently in the initial stages of development include vaccines targeting bacterial factors that are essential for initial attachment and disease progression (such as adhesins, toxins, proteases and siderophores), and small-molecule inhibitors that prevent adhesin-receptor interactions. […] In this Review, we discuss how basic science studies are elucidating the molecular details of the crosstalk that occurs at the host-pathogen interface, as well as the consequences of these interactions for the pathophysiology of UTIs.

• #37 Host–pathogen interactions in urinary tract infection | Nature Reviews Urology

  https://www.nature.com/articles/nrurol.2010.101

  The urinary tract is a common site of bacterial infections; nearly half of all women experience at least one urinary tract infection (UTI) during their lifetime. […] Uropathogenic Escherichia coli and Proteus mirabilis are representative pathogens of uncomplicated and complicated urinary tract infection (UTI), respectively. […] Virulence and fitness factors synthesized by both pathogens include fimbriae, toxins, flagella, iron acquisition systems, and proteins that function in immune evasion. […] Additional factors that contribute to infection include the formation of intracellular bacterial communities by E. coli and the production of urease by P. mirabilis, which can result in urinary stone formation. […] Innate immune responses are induced or mediated by pattern recognition receptors, antimicrobial peptides, and neutrophils; the adaptive immune response to UTI is less well understood.

• #38 The Pathogenesis of Urinary Tract Infections | IntechOpen

  https://www.intechopen.com/chapters/19318

  Adhesins found on the surface of the bacterial membrane are responsible for initial attachment onto urinary tract tissues (Mulvey 2002). […] Adhesins are classified as fimbrial or afimbrial, depending on whether the adhesin is displayed as part of a rigid fimbria or pilus. Fimbriae and pili are surface glycoproteins that function as ligands for glycolipid and glycoprotein receptors on uroepithelial cells. […] After binding to the epithelial surface the activated Fim H adhesins migrate towards deeper urothelial layers and penetrate the cell membrane (Mulvey et al. 2000). Once the uropathogen is intracellular the invasive process continues as bacteria proliferate within the cytosol to form clusters (Anderson et al. 2004b). […] The hosts innate immune response is primarily responsible for providing resistance to the invading uropathogen. Numerous cell types such as neutrophils, macrophages, eosinophils and natural killer cells are activated as the uropathogen invades.

• #39 Urinary Tract Infections: The Current Scenario and Future Prospects

  https://www.mdpi.com/2076-0817/12/4/623

  Most UTIs are caused by Gram-negative and Gram-positive bacteria residing in the colon, such as Escherichia coli, Enterococcus faecalis, Proteus mirabilis, and Klebsiella pneumoniae. […] These uropathogens use different types of adhesins that promote binding and biofilm formation on biotic and abiotic surfaces. […] Biofilm formation by these pathogenic bacteria requires specific virulence factors that play a key role in inducing adhesion to host epithelial cells or catheter materials. […] Bacterial biofilms play an important role in UTIs, being responsible for the persistence of infections that result in recurrence and relapse. […] The main virulence factors involved in host cell adhesion are Type 1 and Type 2 fimbriae, P fimbriae, Dr adhesion, S fimbriae, and F1C fimbriae. […] UPEC strains express a broad spectrum of virulence factors, but their ability to cause UTIs is fundamentally related to their ability to produce a number of adhesins that can facilitate adhesion under different environmental conditions.

• #40 Urinary tract infections: epidemiology, mechanisms of infection and treatment options

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4457377/

  The process of invasion and IBC formation provides UPEC with the ability to survive stringent bottlenecks in the urinary tract, including TLR4-mediated expulsion, umbrella cell exfoliation, ascension to the kidneys, urination and inflammation. […] Importantly, the initial innate host response to UPEC colonization and invasion not only dictates the outcome of the original infection but is also crucial for determining host susceptibility to subsequent infections. […] UPEC secretes high concentrations of -haemolysin (HlyA), which oligomerizes and integrates in the cholesterol-rich microdomains in the host cell membrane in a Ca+-dependent manner. […] This results in pore formation in the umbrella cells and promotes their lysis, which facilitates iron and nutrient acquisition by the bacteria.

• #41 Urinary tract infections: epidemiology, mechanisms of infection and treatment options

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4457377/

  UPEC also secretes cytotoxic necrotizing factor 1 (CNF1), which affects actin remodelling in the host cell through three small RHO GTPases: RAC1, RHOA and cell division control 42 (CDC42). […] The expression of all of these virulence factors is regulated by the quorum sensing system. […] Urease is encoded by several uropathogens, including P. mirabilis, S. saprophyticus, K. pneumoniae and P. aeruginosa, and is important for colonization and persistence during P. mirabilis and S. saprophyticus UTIs. […] The high activity level of the P. mirabilis enzyme induces rapid crystal formation, and these crystals become trapped within the polysaccharides produced by attached bacterial cells, forming crystalline biofilms on catheters. […] These structures also block urine drainage from the ureters, potentially resulting in reflux and promoting progression to pyelonephritis, septicaemia and shock.

• #42 Host–pathogen interactions in urinary tract infection | Nature Reviews Urology

  https://www.nature.com/articles/nrurol.2010.101

  The urinary tract is a common site of bacterial infections; nearly half of all women experience at least one urinary tract infection (UTI) during their lifetime. […] Uropathogenic Escherichia coli and Proteus mirabilis are representative pathogens of uncomplicated and complicated urinary tract infection (UTI), respectively. […] Virulence and fitness factors synthesized by both pathogens include fimbriae, toxins, flagella, iron acquisition systems, and proteins that function in immune evasion. […] Additional factors that contribute to infection include the formation of intracellular bacterial communities by E. coli and the production of urease by P. mirabilis, which can result in urinary stone formation. […] Innate immune responses are induced or mediated by pattern recognition receptors, antimicrobial peptides, and neutrophils; the adaptive immune response to UTI is less well understood.

• #43 Urinary tract infections: epidemiology, mechanisms of infection and treatment options

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4457377/

  UPEC also secretes cytotoxic necrotizing factor 1 (CNF1), which affects actin remodelling in the host cell through three small RHO GTPases: RAC1, RHOA and cell division control 42 (CDC42). […] The expression of all of these virulence factors is regulated by the quorum sensing system. […] Urease is encoded by several uropathogens, including P. mirabilis, S. saprophyticus, K. pneumoniae and P. aeruginosa, and is important for colonization and persistence during P. mirabilis and S. saprophyticus UTIs. […] The high activity level of the P. mirabilis enzyme induces rapid crystal formation, and these crystals become trapped within the polysaccharides produced by attached bacterial cells, forming crystalline biofilms on catheters. […] These structures also block urine drainage from the ureters, potentially resulting in reflux and promoting progression to pyelonephritis, septicaemia and shock.

• #44 Urinary Tract Infections Caused by Uropathogenic Escherichia coli: Mechanisms of Infection and Treatment Options

  https://www.mdpi.com/1422-0067/24/13/10537

  The role of P fimbriae in UTIs is complex and has not yet been fully explored, but a substantial amount of evidence demonstrates its importance to UPEC. […] The number of papIBAHCDJKEFG—10 kbp operons located on pathogenicity islands (PAIs)—depends on various classes of adhesin subunits (ranging from 9 to 12 genes). […] The primary function of siderophores, which are small chelating molecules with a very high affinity for iron, is assumed to be scavenging ferric iron (Fe3+). […] In short, nearly all common iron-acquisition-associated genes are significantly positively selected in UPEC clinical isolates. […] The IBC pathway is a significant target for therapeutic intervention. […] The infection causes the host to have a significant pro-inflammatory reaction, which is followed by an inflow of neutrophils and attempted eradication of bacteria.

• #45 Urinary Tract Infection: Pathogenesis and Outlook

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5159206/

  Upon reaching the urinary bladder, UPEC bind to superficial epithelial (facet) cells in a type 1 pili-dependent manner. […] A subset of adherent bacteria are then internalized into facet cells, a dynamic process that likely relies on the normal cycling of apical membrane segments in these cells. […] Recent data show that UPEC are capable of neutralizing the lysosome, and that this neutralization is sensed by a lysosomal membrane protein termed mucolipin TRP channel 3 (TRPML3), activating pathways that direct exocytosis of UPEC-containing lysosomes. […] Using incompletely defined strategies, UPEC may gain access to the bladder epithelial cell cytoplasm, thereafter developing clonal, biofilm-like masses termed intracellular bacterial communities (IBCs). […] After 16-24 h in murine UTI models, a subset of UPEC in remaining IBCs adopt a neutrophil-resistant, filamentous morphology and escape the IBCs, subsequently re-invading nave bladder epithelial cells.

• #46 Urinary Tract Infections Caused by Uropathogenic Escherichia coli: Mechanisms of Infection and Treatment Options

  https://www.mdpi.com/1422-0067/24/13/10537

  Biofilm and extracellular matrix components have also been implicated as contributors to evading host defenses. In biofilms, bacterial communities are formed and embedded in an extracellular matrix, which is mainly composed of exopolysaccharides, nucleic acids, and proteins. […] The pathogenesis of a UTI starts with the contamination and colonization of the urethral area with UPEC. The bladder epithelium is then invaded by UPEC. Finally, UPEC release toxins that damage host tissues, resulting in upper UTIs. Severe cases can also result in life-threatening illnesses, such as bacteremia, septicemia, and urosepsis.

• #47 The Pathogenesis of Escherichia coli Urinary Tract Infection | IntechOpen

  https://www.intechopen.com/chapters/56154

  UPEC also express outer membrane proteins, such as traT and Iss, which may enhance serum resistance through avoidance of complement killing. Bacteria are killed by normal human serum through the lytic activity of the complement system. Resistance of E. coli to killing by serum results from the individual or combined effects of capsular polysaccharide, O-polysaccharide side chains, and surface proteins. […] A wide range of UPEC VFs have been established epidemiologically or experimentally as being important in UTI pathogenesis. No single VF profile has been proven to be important in causing any particular UTI syndrome. Indeed, studies have suggested that UTI pathogenesis is multiply determined. Thus, intervention strategies based on VF genes might have to involve multiple targets, which would offer the extra advantage of protection against a wide range of UTI syndromes.

• #48 :: Immune Network ::

  https://www.immunenetwork.org/DOIx.php?id=10.4110/in.2024.24.e31

  Urinary tract infections (UTIs) represent one of the most prevalent bacterial infections globally, manifesting in diverse clinical phenotypes with varying degrees of severity and complications. The mechanisms underlying UTIs are gradually being elucidated, leading to an enhanced understanding of the immune responses involved. Innate immune cells play a crucial defensive role against uropathogenic bacteria through various mechanisms. […] Despite their significant contributions to host defense, these cells often fail to achieve complete clearance of uropathogens, necessitating the frequent prescription of antibiotics for UTI patients. However, the persistence of infections and related pathological symptoms in the absence of innate immune cells in animal models underscore the importance of innate immunity in UTIs. Therefore, the host protective functions of innate immune cells, including neutrophils, macrophages, mast cells, NK cells, innate lymphoid cells, and T cells, are delicately coordinated and timely regulated by a variety of cytokines to ensure successful pathogen clearance.

• #49 Pathophysiology of an UTI | Urinary Tract Infection Case Study

  https://u.osu.edu/utieducation/pathophysiology-of-uti/

  In normal healthy individuals, there are several mechanisms that attempt to prevent bacteria from invading the bladder or progressing up through the upper urinary tracts. These mechanisms usually work together to prevent infection and they include: […] If bacteria were to successfully invade, the immune system recruits toll-like receptors (TLR4) which recognize the pathogen and further recruits neutrophils and macrophages to induce phagocytosis. The ability of the pathogen to produce infection is influenced by the virulence of the specific pathogen and individuals specific immune response. If the immune system does not respond quick enough, the pathogen may be able to excessively multiply and inundate the individuals defense mechanism, causing a UTI (McCance Huether, 2019). […] Urinary tract infections are caused by bacterium that invade the urinary epithelium cells causing irritation and inflammation of these cells. The infection can start in the urethra and can progress its way up to the bladder, ureters, or kidney. Infection of the urethra or bladder is known as a lower urinary tract infection while infection of the ureters, renal pelvis or kidney tissue constitutes as a upper urinary tract infection.

• #50 Urinary Tract Infection (UTI) and Cystitis (Bladder Infection) in Females: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/233101-overview

  Frequent and complete voiding has been associated with a reduction in the incidence of UTI. Normally, a thin film of urine remains in the bladder after emptying, and any bacteria present are removed by the mucosal cell production of organic acids. […] If the defense mechanisms of the lower urinary tract fail, upper tract or kidney involvement occurs and is termed pyelonephritis. Host defenses at this level include local leukocyte phagocytosis and renal production of antibodies that kill bacteria in the presence of complement. […] In general, there are 3 main mechanisms responsible for UTIs: colonization with ascending spread, hematogenous spread, periurogenital spread. […] Uropathogenic bacteria, derived from a subset of fecal flora, have traits that enable adherence, growth, and resistance of host defenses. These traits facilitate colonization and infection of the urinary tract.

• #51 Urinary Tract Infection (UTI) and Cystitis (Bladder Infection) in Females: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/233101-overview

  Secretory defenses help promote bacterial clearance and prevent adherence. Secretory immunoglobulin A (IgA) reduces attachment and invasion of bacteria in the urinary tract. Women who are nonsecretors of the ABH blood antigens appear to be at higher risk for recurrent UTIs; this may occur because of a lack of specific glycosyltransferases that modify epithelial surface glycolipids, allowing E coli to bind to them better. […] Urine itself has several antibacterial features that suppress UTIs. Specifically, the pH, urea concentration, osmolarity, and various organic acids prevent most bacteria from surviving in the urinary tract.

• #52 Urinary tract infection Information | Mount Sinai – New York

  https://www.mountsinai.org/health-library/report/urinary-tract-infection

  Urinary tract infections (UTIs) are a common type of infection typically caused by bacteria (most often E. coli). Cystitis is an infection of the bladder (lower urinary tract infection) caused by bacteria that travel up the urethra to the bladder. Pyelonephritis is an infection of the kidneys and ureters (upper urinary tract infection), a much more serious condition. […] Nearly 95% of cases of UTIs are caused by bacteria that typically multiply at the opening of the urethra and travel up to the bladder. Much less often, bacteria spread to the kidney from the bloodstream. […] Infection does not always occur when bacteria are introduced into the bladder. A number of defense systems protect the urinary tract against infection-causing bacteria: Urine functions as an antiseptic, washing potentially harmful bacteria out of the body during normal urination. (Urine is normally sterile, that is, free of bacteria, viruses, and fungi.) Urine is also slightly acidic (low pH), which also inhibits bacterial growth.

• #53 Urinary Tract Infection (UTI) and Cystitis (Bladder Infection) in Females: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/233101-overview

  Secretory defenses help promote bacterial clearance and prevent adherence. Secretory immunoglobulin A (IgA) reduces attachment and invasion of bacteria in the urinary tract. Women who are nonsecretors of the ABH blood antigens appear to be at higher risk for recurrent UTIs; this may occur because of a lack of specific glycosyltransferases that modify epithelial surface glycolipids, allowing E coli to bind to them better. […] Urine itself has several antibacterial features that suppress UTIs. Specifically, the pH, urea concentration, osmolarity, and various organic acids prevent most bacteria from surviving in the urinary tract.

• #54 An Update on Urinary Tract Infection

  https://www.jrmds.in/articles/an-update-on-urinary-tract-infection-61386.html

  Urinary tract infections are the commonest infection encountered in the community. […] Urine is a sterile fluid. The bacteria can invade and cause UTI via two major routes. […] Ascending route is the commonest route of infection in females. Catherterization and cystoscopy can cause UTI in both males and females by ascending route. Descending route of infection is caused by hematogenous spread as result of bacteremia. […] Immune system- Lipopolysaccharide of bacteria activates the host cell and release cytokines such as TNF and TNF, activation of complement system. […] Tamm-Horsfall protein or uromucoid serves as anti-adhesion factor by binding to E. coli, expressing type I fimbriae. […] The Following factors help in the development of UTI. […] UTI is more common in females because of short urethra that opens into the moist introitus which is colonized by bacteria. For many women sexual intercourse precipitates UTI. […] Virulence Factors for E. coli. Fimbria which binds on uroepithelium persists within the urinary tract. Three types are Type S fimbriae, Type P fimbriae and Type D fimbriae.

• #55 Researchers Uncover How Our Body Fight UTIs

  https://www.genengnews.com/news/researchers-uncover-how-our-body-fight-utis/

  Uromodulin filaments (blue) envelop an E. coli cell, thus preventing the pathogen’s pili from docking on the cell walls in the urinary tract and causing an infection. […] Urinary tract infections (UTIs) can be treated by antibiotics, but may be fatal if left untreated. These infections are usually caused by what are known as uropathogenic E. coli bacteria when they bind to the cells of the bladder, ureter, or urethra with their pili. […] The body naturally produces a protein called uromodulin that aids in fighting UTIs. However, the exact process by which uromodulin prevents inflammation has never been understood. […] Uromodulin is the most abundant protein in human urine and forms filaments that antagonize the adhesion of uropathogens; however, filament structure and mechanism of protection remain poorly understood.

• #56 Urinary tract infection Information | Mount Sinai – New York

  https://www.mountsinai.org/health-library/report/urinary-tract-infection

  The bacteria that cause kidney infections (pyelonephritis) are generally the same bacteria that cause cystitis. There is some evidence that the E. coli strains causing pyelonephritis are more virulent (able to spread and cause illness). […] Changes in the amount or type of acid within the genital and urinary tracts contribute to lowering the resistance to infection. For example, beneficial organisms called lactobacilli increase the acidic environment in the female urinary tract and thereby reduce the risk of infection.

• #57 :: Immune Network ::

  https://www.immunenetwork.org/DOIx.php?id=10.4110/in.2024.24.e31

  Urinary tract infections (UTIs) represent one of the most prevalent bacterial infections globally, manifesting in diverse clinical phenotypes with varying degrees of severity and complications. The mechanisms underlying UTIs are gradually being elucidated, leading to an enhanced understanding of the immune responses involved. Innate immune cells play a crucial defensive role against uropathogenic bacteria through various mechanisms. […] Despite their significant contributions to host defense, these cells often fail to achieve complete clearance of uropathogens, necessitating the frequent prescription of antibiotics for UTI patients. However, the persistence of infections and related pathological symptoms in the absence of innate immune cells in animal models underscore the importance of innate immunity in UTIs. Therefore, the host protective functions of innate immune cells, including neutrophils, macrophages, mast cells, NK cells, innate lymphoid cells, and T cells, are delicately coordinated and timely regulated by a variety of cytokines to ensure successful pathogen clearance.

• #58 :: Immune Network ::

  https://www.immunenetwork.org/DOIx.php?id=10.4110/in.2024.24.e31

  The urinary bladder harbors a diverse array of innate immune cells, including tissue-resident innate immune cells such as macrophages, innate lymphoid cells (ILCs), dendritic cells, mast cells, and T cells, which play defensive roles. […] However, when these immune cells are insufficient to deal with rapidly proliferating bacterial infections, the body mobilizes non-resident immune effector cells from the bloodstream, such as neutrophils, monocytes, and NK cells, to actively participate in host defense. […] The dynamics of neutrophils in response to bacterial infection in the bladder have been systematically investigated using murine models. Neutrophil infiltration typically peaks at 6 h post-infection, followed by a gradual decline in influx attributed to a reduction in bacterial load or response to anti-inflammatory cytokines.

• #59 :: Immune Network ::

  https://www.immunenetwork.org/DOIx.php?id=10.4110/in.2024.24.e31

  The robust phagocytic capabilities of macrophages and dendritic cells are activated upon the infiltration of uropathogens subsequent to the breach of superficial epithelial cells within the bladder mucosa. […] Their sentinel role in pathogen recognition and direct killing mediated by pattern recognition receptors (PRRs) is key to reducing the initial bacterial burden during the early stages of infection. […] Following recognition of UPEC through TLRs on bladder epithelial cells, IL-8 secretion induces neutrophil recruitment to the infected epithelial cells. […] The defensive function of macrophages against UPEC has been demonstrated in experiments depleting monocytes/macrophages using clodronate liposomes. […] Upon recognition of pathogens, Ly6C macrophages secrete chemokines, recruiting neutrophils and Ly6C+ monocytes (or macrophages) into the bladder’s lamina propria.

• #60 Host–pathogen interactions in urinary tract infection | Nature Reviews Urology

  https://www.nature.com/articles/nrurol.2010.101

  Host factors TLR4 and CXCR1 are implicated in disease outcome and susceptibility, respectively; low levels of TLR4 are associated with asymptomatic bacteriuria; low levels of CXCR1 are associated with increased incidence of acute pyelonephritis. […] Current research is focused on the identification of additional virulence factors and therapeutic or prophylactic targets that might be used in the generation of vaccines against both uropathogens.

• #61 Urinary Tract Infection: Pathogenesis and Outlook

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5159206/

  Although this work has provided broad insight into the metabolic activities required to cause UTI, we are on the verge of being able to specifically interrogate UPEC populations in defined niches and times during infection. […] Comparatively less is known about the molecular pathogenesis of infection in the kidney. […] Attenuation in mouse kidney infections has been observed with UPEC mutants lacking specific virulence factors, such as type 1 pili, P pili, flagella, and cytotoxic necrotizing factor 1 (CNF1). […] The importance of this neutrophil influx in controlling UPEC infection has been well established. […] The formation of IBCs is a key means by which bacteria subvert neutrophil activity, as arriving neutrophils accurately locate IBC-bearing facet cells but cannot access the bacteria within.

• #62 :: Immune Network ::

  https://www.immunenetwork.org/DOIx.php?id=10.4110/in.2024.24.e31

  The urinary bladder harbors a diverse array of innate immune cells, including tissue-resident innate immune cells such as macrophages, innate lymphoid cells (ILCs), dendritic cells, mast cells, and T cells, which play defensive roles. […] However, when these immune cells are insufficient to deal with rapidly proliferating bacterial infections, the body mobilizes non-resident immune effector cells from the bloodstream, such as neutrophils, monocytes, and NK cells, to actively participate in host defense. […] The dynamics of neutrophils in response to bacterial infection in the bladder have been systematically investigated using murine models. Neutrophil infiltration typically peaks at 6 h post-infection, followed by a gradual decline in influx attributed to a reduction in bacterial load or response to anti-inflammatory cytokines.

• #63 :: Immune Network ::

  https://www.immunenetwork.org/DOIx.php?id=10.4110/in.2024.24.e31

  The robust phagocytic capabilities of macrophages and dendritic cells are activated upon the infiltration of uropathogens subsequent to the breach of superficial epithelial cells within the bladder mucosa. […] Their sentinel role in pathogen recognition and direct killing mediated by pattern recognition receptors (PRRs) is key to reducing the initial bacterial burden during the early stages of infection. […] Following recognition of UPEC through TLRs on bladder epithelial cells, IL-8 secretion induces neutrophil recruitment to the infected epithelial cells. […] The defensive function of macrophages against UPEC has been demonstrated in experiments depleting monocytes/macrophages using clodronate liposomes. […] Upon recognition of pathogens, Ly6C macrophages secrete chemokines, recruiting neutrophils and Ly6C+ monocytes (or macrophages) into the bladder’s lamina propria.

• #64 :: Immune Network ::

  https://www.immunenetwork.org/DOIx.php?id=10.4110/in.2024.24.e31

  The urinary bladder harbors a diverse array of innate immune cells, including tissue-resident innate immune cells such as macrophages, innate lymphoid cells (ILCs), dendritic cells, mast cells, and T cells, which play defensive roles. […] However, when these immune cells are insufficient to deal with rapidly proliferating bacterial infections, the body mobilizes non-resident immune effector cells from the bloodstream, such as neutrophils, monocytes, and NK cells, to actively participate in host defense. […] The dynamics of neutrophils in response to bacterial infection in the bladder have been systematically investigated using murine models. Neutrophil infiltration typically peaks at 6 h post-infection, followed by a gradual decline in influx attributed to a reduction in bacterial load or response to anti-inflammatory cytokines.

• #65 Research : WUSTL Hultgren Lab

  https://hultgrenlab.wustl.edu/research/urinary-tract-infection/

  We have also shown that Klebsiella UTI is dependent on FimH mediated colonization and IBC formation. […] We are investigating the mechanism of UPEC intra-host growth in in vitro infection model by using primary bladder cells and manipulating the host signaling pathways. […] The host response to UPEC infection is a complex process that involves exfoliation of epithelial cells, release of cytokines and chemokines and the influx of inflammatory cells into the bladder. […] The resultant shedding of infected superficial facet cells is an important defense to expel bacteria from the bladder in the urine stream. However, this shedding also exposes underlying epithelial cells to infection. […] These COX2-dependent host responses are crucial for the associated mucosal damage that ensues during infection.

• #66 Research : WUSTL Hultgren Lab

  https://hultgrenlab.wustl.edu/research/urinary-tract-infection/

  We have also shown that Klebsiella UTI is dependent on FimH mediated colonization and IBC formation. […] We are investigating the mechanism of UPEC intra-host growth in in vitro infection model by using primary bladder cells and manipulating the host signaling pathways. […] The host response to UPEC infection is a complex process that involves exfoliation of epithelial cells, release of cytokines and chemokines and the influx of inflammatory cells into the bladder. […] The resultant shedding of infected superficial facet cells is an important defense to expel bacteria from the bladder in the urine stream. However, this shedding also exposes underlying epithelial cells to infection. […] These COX2-dependent host responses are crucial for the associated mucosal damage that ensues during infection.

• #67 :: Immune Network ::

  https://www.immunenetwork.org/DOIx.php?id=10.4110/in.2024.24.e31

  The expression of uroplakin by bladder umbrella cells facilitates the attachment of UPEC fimbriae, thereby promoting infection, with the attached UPEC serving as a reservoir for persistent infection within the epithelial cells. […] Bladder epithelial cells play a role in inhibiting the formation of intracellular bacterial communities (IBCs) and ultimately contributing to direct UPEC clearance. […] Bladder epithelial cells not only defend against bacteria through the influx of immune cells but also exert a physical defense mechanism by expelling pathogens outside the cell. […] Despite these initial responses, pathogens adapt to colonize and invade epithelial cells, prompting various components of the innate immune system to act, with neutrophils playing a pivotal role. […] Understanding why bacteria causing intracellular infections evade immune cells involved in adaptive immunity requires the establishment of appropriate animal models and the use of various immunological analysis methods.

• #68 Urinary Tract Infection: Pathogenesis and Outlook

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5159206/

  UPEC can subvert and delay the innate immune response in multiple ways. […] While robust innate defenses are able to repel most bacterial challenges, this inflammatory response may represent a double-edged sword. […] Understanding the basis of functional adaptive immunity against UTI could have major implications for recurrent UTIs and vaccine development. […] Contemporary development of novel UTI therapeutics has focused on interfering with pathogen binding to bladder epithelium or other key pathogen processes, the development of vaccines based on bacterial components, as well as the modulation of host responses. […] Successful vaccination against UPEC and other uropathogens could have monumental impact on the lives of those at risk for complicated UTIs or who suffer from recurring episodes. […] Advanced, more efficacious exfoliants are being designed to unearth these quiescent reservoirs. […] As the urinary microbiome is more extensively defined, we will have to account for it when considering the pathogenesis of UTI, as well as when choosing therapies for symptomatic patients.

• #69 Urinary Tract Infections Caused by Uropathogenic Escherichia coli: Mechanisms of Infection and Treatment Options

  https://www.mdpi.com/1422-0067/24/13/10537

  Biofilm and extracellular matrix components have also been implicated as contributors to evading host defenses. In biofilms, bacterial communities are formed and embedded in an extracellular matrix, which is mainly composed of exopolysaccharides, nucleic acids, and proteins. […] The pathogenesis of a UTI starts with the contamination and colonization of the urethral area with UPEC. The bladder epithelium is then invaded by UPEC. Finally, UPEC release toxins that damage host tissues, resulting in upper UTIs. Severe cases can also result in life-threatening illnesses, such as bacteremia, septicemia, and urosepsis.

• #70 Urinary Tract Infection: Pathogenesis and Outlook

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5159206/

  Upon reaching the urinary bladder, UPEC bind to superficial epithelial (facet) cells in a type 1 pili-dependent manner. […] A subset of adherent bacteria are then internalized into facet cells, a dynamic process that likely relies on the normal cycling of apical membrane segments in these cells. […] Recent data show that UPEC are capable of neutralizing the lysosome, and that this neutralization is sensed by a lysosomal membrane protein termed mucolipin TRP channel 3 (TRPML3), activating pathways that direct exocytosis of UPEC-containing lysosomes. […] Using incompletely defined strategies, UPEC may gain access to the bladder epithelial cell cytoplasm, thereafter developing clonal, biofilm-like masses termed intracellular bacterial communities (IBCs). […] After 16-24 h in murine UTI models, a subset of UPEC in remaining IBCs adopt a neutrophil-resistant, filamentous morphology and escape the IBCs, subsequently re-invading nave bladder epithelial cells.

• #71 Research : WUSTL Hultgren Lab

  https://hultgrenlab.wustl.edu/research/urinary-tract-infection/

  In our interdisciplinary research program, we have combined clinical and basic science approaches to detail a highly complex acute pathogenic cycle for uropathogenic Escherichia coli (UPEC), the most common causative agent of UTIs and the host response to infection. […] Using our mouse model of urinary tract infection, we have delineated an acute pathogenic cascade that initiates when UPEC enter the mammalian bladder. Using type 1 pili with its adhesin, FimH, UPEC adhere to mannosylated residues on the bladder surface and invade into the superficial epithelial cells of the bladder. UPEC then enter the cytoplasm and rapidly replicate to form large intracellular bacterial communities (IBCs), with 104 bacteria per mature IBC within a few hours of invasion. […] This pathway allows UPEC to gain a foothold in the host, building up in numbers in an intracellular niche protected from much of the host immune response. Further, UPEC filamentation upon fluxing from the IBC allows UPEC to resist the action of neutrophils in the bladder lumen.

• #72 Urinary Tract Infections Caused by Uropathogenic Escherichia coli: Mechanisms of Infection and Treatment Options

  https://www.mdpi.com/1422-0067/24/13/10537

  Biofilm and extracellular matrix components have also been implicated as contributors to evading host defenses. In biofilms, bacterial communities are formed and embedded in an extracellular matrix, which is mainly composed of exopolysaccharides, nucleic acids, and proteins. […] The pathogenesis of a UTI starts with the contamination and colonization of the urethral area with UPEC. The bladder epithelium is then invaded by UPEC. Finally, UPEC release toxins that damage host tissues, resulting in upper UTIs. Severe cases can also result in life-threatening illnesses, such as bacteremia, septicemia, and urosepsis.

• #73 Antibiotic Resistant UTI | Treatments for Urinary Tract Infections

  https://www.antibioticresearch.org.uk/patient-support/specific-infections/urinary-tract-infections-utis/

  The main difference between a regular UTI and an antibiotic-resistant UTI is that the medicines usually used to treat such infections do not often work against antibiotic-resistant UTIs. […] The bacteria become harder to eradicate, even when taking powerful antibiotics, as they form a biofilm. This is where the colonies of resistant bacteria form a protective layer around themselves, making it even more difficult for antibiotics to reach and kill them. […] An antibiotic resistant UTI can then become a chronic condition and can often cause frequently recurring outbreaks of infection, with an increased risk of serious kidney infection (pyelonephritis) and even sepsis. […] If resistant organisms are discovered they are often found to be ESBL E. coli or ESBL Klebsiella. If you have a UTI with either of these resistant bacteria, you will probably be treated in hospital by an infectious disease doctor and their team. […] These are considered last resort antibiotics which are kept especially for those highly resistant bacterial infections.

• #74 Urinary Tract Infection: Pathogenesis and Outlook

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5159206/

  UPEC can subvert and delay the innate immune response in multiple ways. […] While robust innate defenses are able to repel most bacterial challenges, this inflammatory response may represent a double-edged sword. […] Understanding the basis of functional adaptive immunity against UTI could have major implications for recurrent UTIs and vaccine development. […] Contemporary development of novel UTI therapeutics has focused on interfering with pathogen binding to bladder epithelium or other key pathogen processes, the development of vaccines based on bacterial components, as well as the modulation of host responses. […] Successful vaccination against UPEC and other uropathogens could have monumental impact on the lives of those at risk for complicated UTIs or who suffer from recurring episodes. […] Advanced, more efficacious exfoliants are being designed to unearth these quiescent reservoirs. […] As the urinary microbiome is more extensively defined, we will have to account for it when considering the pathogenesis of UTI, as well as when choosing therapies for symptomatic patients.

• #75 Urinary Tract Infection: Pathogenesis and Outlook

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5159206/

  Some of these bacteria will go on to infect immature bladder epithelium which is exposed after exfoliation, later forming quiescent intracellular reservoirs, which avoid immune clearance and resist systemic antibiotic treatment. […] These persistent UPEC may re-emerge, in response to currently undefined signals, to cause the recurrent cystitis that is so clinically common. […] A significant gap in our understanding is the mechanism by which UPEC escape the initial vacuole (after internalization) to reach the cytoplasm, where the IBC is formed. […] Following escape into the cytoplasm, the bacteria find themselves occupying an environment very different from the nutrient-poor bladder lumen. […] Transcriptomic analyses of UPEC in different models have suggested that various metabolic pathways are essential for pathogenesis; these include sialic acid transport/metabolism, gluconeogenesis, the tricarboxylic acid (TCA) cycle, iron uptake, ethanolamine and phosphate metabolism, as well as amino acid metabolism.

• #76 Urinary Tract Infections: The Current Scenario and Future Prospects

  https://www.mdpi.com/2076-0817/12/4/623

  The spread of UTIs is closely linked to the effectiveness of a number of strategies that uropathogens have developed to adhere to and invade host tissues. […] Complicating factors that are involved in the progression of UTI are biofilms, urinary stasis due to obstruction, and catheters. […] The risk of UTI is influenced by a wide range of intrinsic and acquired factors, such as urinary retention, vesicoureteral reflux, frequent sexual intercourse, prostate gland enlargement, vulvovaginal atrophy, and family history. […] Uropathogenic E. coli (UPEC) is the most common causative agent of both uUTIs and cUTIs. […] The ability of different uropathogens to successfully adhere to and colonize the epithelium of the lower urinary tract is related to their ability to express specific virulence factors.

• #77 5 tips to prevent a urinary tract infection – Mayo Clinic Health System

  https://www.mayoclinichealthsystem.org/hometown-health/speaking-of-health/5-tips-to-prevent-a-urinary-tract-infection

  A urinary tract infection, also called a UTI, is an infection that occurs in the urinary system. This could include the urethra, bladder, ureters and kidneys. Most infections involve the bladder and urethra, known as the lower urinary tract. […] Women are at greater risk for a UTI because the urethra is shorter than in men, so it’s easier for bacteria to travel to the bladder. UTIs also are more common in postmenopausal women because low estrogen levels change vaginal and urethral tissue to increase the risk of infection. […] Risk factors for recurrent UTIs include: Frequent sexual intercourse, which increases the likelihood of bacteria entering the urethra and bladder. Using spermicide with or without a diaphragm, as this can harm protective bacteria in the urinary tract that defend against infection. Urinary retention or incomplete bladder emptying caused by medications; narrowing of the urethra; prolapse of the bladder, uterus or vagina; neurological conditions; or sometimes unknown reasons. Vaginal atrophy, which is a postmenopausal condition caused by decreased estrogen levels. Genetics, especially the inherited genes that regulate the body’s immune response to infections.

• #78 Causes, Pathogens, and Risk Faktors of Urinary Tract Infection

  https://www.urology-textbook.com/urinary-tract-infection-causes.html

  Bacteria can invade the urinary tract by ascending from the urethra, hematogenous spread, lymphatic spread and invasion via the neighboring organs. […] Ascending infections are the most common cause of urinary tract infections. Because the female urethra is short and intestinal bacteria tend to colonize the perineum and vulva, women are more prone to UTIs than men. […] Hematogenous-caused urinary tract infections are rare: urogenital tuberculosis, renal abscess, perinephric abscess, or epididymitis. […] Lymphatic causes of UTI are rare and speculative; bacteria may spread to the prostate, bladder, and female internal genital organs in case of severe bowel inflammation. […] Urinary tract infections may be causes by invasion from neighboring organs: through intraperitoneal abscess, pelvic inflammatory disease, bowel fistula (Crohn disease, diverticulitis, cancer), vesicovaginal fistula.

• #79 5 tips to prevent a urinary tract infection – Mayo Clinic Health System

  https://www.mayoclinichealthsystem.org/hometown-health/speaking-of-health/5-tips-to-prevent-a-urinary-tract-infection

  A urinary tract infection, also called a UTI, is an infection that occurs in the urinary system. This could include the urethra, bladder, ureters and kidneys. Most infections involve the bladder and urethra, known as the lower urinary tract. […] Women are at greater risk for a UTI because the urethra is shorter than in men, so it’s easier for bacteria to travel to the bladder. UTIs also are more common in postmenopausal women because low estrogen levels change vaginal and urethral tissue to increase the risk of infection. […] Risk factors for recurrent UTIs include: Frequent sexual intercourse, which increases the likelihood of bacteria entering the urethra and bladder. Using spermicide with or without a diaphragm, as this can harm protective bacteria in the urinary tract that defend against infection. Urinary retention or incomplete bladder emptying caused by medications; narrowing of the urethra; prolapse of the bladder, uterus or vagina; neurological conditions; or sometimes unknown reasons. Vaginal atrophy, which is a postmenopausal condition caused by decreased estrogen levels. Genetics, especially the inherited genes that regulate the body’s immune response to infections.

• #80 Recurrent Urinary Tract Infections in Women: Diagnosis and Management | AAFP

  https://www.aafp.org/pubs/afp/issues/2010/0915/p638.html

  Diabetes mellitus, neurologic conditions, chronic institutional residence, and chronic indwelling urinary catheterization are important predisposing factors for complicated UTIs. […] In affected patients, organisms that are typically less virulent may cause marked illness, although E. coli infection remains the most common organism in nearly all patient groups. […] The strongest risk factor for recurrent UTIs in young women is frequency of sexual intercourse. […] A variety of factors place patients at risk of complicated UTIs, and recurrent infection is common. […] The principles of treating recurrent complicated UTIs include early use of broad-spectrum antibiotics, with adjustment of antibiotic coverage based on culture results, and attempts to relieve any existing urinary obstruction based on the results of imaging studies.

• #81 Urinary Tract Infections During Pregnancy | AAFP

  https://www.aafp.org/pubs/afp/issues/2000/0201/p713.html

  Urinary tract infections are common during pregnancy, and the most common causative organism is Escherichia coli. Asymptomatic bacteriuria can lead to the development of cystitis or pyelonephritis. […] This article briefly examines the pathogenesis and bacteriology of UTIs during pregnancy, as well as patient-oriented outcomes. We review the diagnosis and treatment of asymptomatic bacteriuria, acute cystitis and pyelonephritis, plus the unique issues of group B streptococcus and recurrent infections. […] Pregnant women are at increased risk for UTIs. Beginning in week 6 and peaking during weeks 22 to 24, approximately 90 percent of pregnant women develop ureteral dilatation, which will remain until delivery (hydronephrosis of pregnancy). Increased bladder volume and decreased bladder tone, along with decreased ureteral tone, contribute to increased urinary stasis and ureterovesical reflux. […] Additionally, the physiologic increase in plasma volume during pregnancy decreases urine concentration. Up to 70 percent of pregnant women develop glycosuria, which encourages bacterial growth in the urine. Increases in urinary progestins and estrogens may lead to a decreased ability of the lower urinary tract to resist invading bacteria. This decreased ability may be caused by decreased ureteral tone or possibly by allowing some strains of bacteria to selectively grow. […] These factors may all contribute to the development of UTIs during pregnancy.

• #82 Is It a Urinary Tract Infection (UTI)? What Women Should Know > News > Yale Medicine

  https://www.yalemedicine.org/news/urinary-tract-infection-uti

  A UTI is a bacterial infection that affects the urinary tract. Most are caused by Escherichia coli (E. coli), although other bacteria are sometimes responsible. […] UTIs occur when bacteria enter the urinary tract through the urethra, the thin tube that runs from your bladder to the opening where urine exits your body. UTIs may affect the urethra, bladder, kidneys, or ureters, which are thin tubes that connect the kidneys to the bladder. […] Its thought that the rectum and the stool is a reservoir for uropathogens, which are bacteria that can cause infections in the urinary tract, Dr. Rickey says. […] Because UTIs are bacterial infections, they are most often treated with antibiotics. […] Vaginal estrogen likely works by restoring the vaginal pH and microbiome, Dr. Rickey says, while cranberry and D-mannose help prevent certain bacteria, including E. coli bacteria, from attaching to surfaces within the urinary tract. Because most UTIs are caused by E. coli, these supplements may be helpful for controlling UTIs. However, more research is needed to determine the mechanism of action and effectiveness.

• #83 Urinary Tract Infections (UTIs) – Nephrology – Diseases – McMaster Textbook of Internal Medicine

  https://empendium.com/mcmtextbook/chapter/B31.II.14.8.

  The term urinary tract infection (UTI) is defined as the presence of microorganisms in the urinary tract above the bladder sphincter in symptomatic patients. […] Physiologically, the urinary tract remains sterile, with the exception of the distal part of the urethra, which is colonized by saprophytic coagulase-negative staphylococci (eg, Staphylococcus epidermidis), vaginal coccobacilli (Gardnerella [previously known as Haemophilus] vaginalis), nonhemolytic streptococci, corynebacteria, and lactobacilli. Pathogenic colonization of the urinary tract is predominantly ascending. The first stage of an ascending UTI involves colonization of the urethral opening by uropathogenic bacteria; women are more susceptible to this process due to the constant presence of uropathogenic microorganisms in the vaginal vestibule, as well as due to the closer proximity of the urethral opening to the anus and the short urethra. Sexual intercourse can facilitate ascending colonization in female patients. Subsequently, the microorganisms enter the bladder. In immunocompetent individuals, microbial colonization typically does not extend beyond the bladder. The risk of kidney involvement increases as the bacteria continue to persist in the bladder or in the presence of risk factors. Hematogenous and lymphatic spread of infection is responsible for only ~2% of all cases of UTI, but these have the most severe course and usually affect patients who are seriously ill, immunodeficient, or both. […] Risk factors for developing a complicated course of UTI: Urinary retention, nephrolithiasis, vesicoureteral reflux, catheterization, diabetes mellitus (particularly poorly controlled), advanced age, pregnancy, postpartum period, hospitalization for unrelated reasons.

• #84 Urinary Tract Infections During Pregnancy | AAFP

  https://www.aafp.org/pubs/afp/issues/2000/0201/p713.html

  Urinary tract infections are common during pregnancy, and the most common causative organism is Escherichia coli. Asymptomatic bacteriuria can lead to the development of cystitis or pyelonephritis. […] This article briefly examines the pathogenesis and bacteriology of UTIs during pregnancy, as well as patient-oriented outcomes. We review the diagnosis and treatment of asymptomatic bacteriuria, acute cystitis and pyelonephritis, plus the unique issues of group B streptococcus and recurrent infections. […] Pregnant women are at increased risk for UTIs. Beginning in week 6 and peaking during weeks 22 to 24, approximately 90 percent of pregnant women develop ureteral dilatation, which will remain until delivery (hydronephrosis of pregnancy). Increased bladder volume and decreased bladder tone, along with decreased ureteral tone, contribute to increased urinary stasis and ureterovesical reflux. […] Additionally, the physiologic increase in plasma volume during pregnancy decreases urine concentration. Up to 70 percent of pregnant women develop glycosuria, which encourages bacterial growth in the urine. Increases in urinary progestins and estrogens may lead to a decreased ability of the lower urinary tract to resist invading bacteria. This decreased ability may be caused by decreased ureteral tone or possibly by allowing some strains of bacteria to selectively grow. […] These factors may all contribute to the development of UTIs during pregnancy.

• #85 Urinary Tract Infections (UTIs) – Nephrology – Diseases – McMaster Textbook of Internal Medicine

  https://empendium.com/mcmtextbook/chapter/B31.II.14.8.

  The term urinary tract infection (UTI) is defined as the presence of microorganisms in the urinary tract above the bladder sphincter in symptomatic patients. […] Physiologically, the urinary tract remains sterile, with the exception of the distal part of the urethra, which is colonized by saprophytic coagulase-negative staphylococci (eg, Staphylococcus epidermidis), vaginal coccobacilli (Gardnerella [previously known as Haemophilus] vaginalis), nonhemolytic streptococci, corynebacteria, and lactobacilli. Pathogenic colonization of the urinary tract is predominantly ascending. The first stage of an ascending UTI involves colonization of the urethral opening by uropathogenic bacteria; women are more susceptible to this process due to the constant presence of uropathogenic microorganisms in the vaginal vestibule, as well as due to the closer proximity of the urethral opening to the anus and the short urethra. Sexual intercourse can facilitate ascending colonization in female patients. Subsequently, the microorganisms enter the bladder. In immunocompetent individuals, microbial colonization typically does not extend beyond the bladder. The risk of kidney involvement increases as the bacteria continue to persist in the bladder or in the presence of risk factors. Hematogenous and lymphatic spread of infection is responsible for only ~2% of all cases of UTI, but these have the most severe course and usually affect patients who are seriously ill, immunodeficient, or both. […] Risk factors for developing a complicated course of UTI: Urinary retention, nephrolithiasis, vesicoureteral reflux, catheterization, diabetes mellitus (particularly poorly controlled), advanced age, pregnancy, postpartum period, hospitalization for unrelated reasons.

• #86 Urinary Tract Infection, UTI – Pathogenesis, Route of Infection

  https://studymicrobio.com/urinary-tract-infection-uti-pathogenesis-route-of-infection/

  In hospitalized patients, soon patients are colonized with bacteria endemic to the institution, often gram-negative aerobic and facultative bacilli carrying resistance markers. […] With the insertion of a catheter, bacteria may be pushed along the urethra into the bladder. Infection may occur with an indwelling catheter, migrating along the track between the catheter and urethral mucosa, and gaining access to the bladder. Approximately 10-30% of catheterized patients will develop bacteriuria. […] Urinary Tract Infection (UTI) may also occur by the hematogenous or blood-borne route. The hematogenous spread usually occurs as a result of bacteremia. Any systematic infection can lead to seeding of the kidneys, but only certain microorganisms such as S. aureus or Salmonella spp. are invasive.

• #87 Urinary Tract Infections: The Current Scenario and Future Prospects

  https://www.mdpi.com/2076-0817/12/4/623

  Urinary tract infections (UTIs) begin when gut-resident uropathogens colonize the urethra and subsequently the bladder through the action of specific adhesins. […] If the host’s inflammatory response fails to eliminate all bacteria, they begin to multiply, producing toxins and enzymes that promote their survival. […] Subsequent colonization of the kidneys can evolve into bacteremia if the pathogen crosses the kidney epithelial barrier. […] In complicated UTIs, infection by uropathogens is followed by bladder compromise, which occurs with catheterization. […] Uropathogens, through the expression of fibrinogen-binding proteins, bind to the catheter. […] Bacteria also multiply as a result of biofilm protection, and if the infection is left untreated, it can progress to pyelonephritis and bacteremia.

• #88 Causes, Pathogens, and Risk Faktors of Urinary Tract Infection

  https://www.urology-textbook.com/urinary-tract-infection-causes.html

  Uropathogenic bacteria can invade into urothelial cells and form an intracellular bacterial community (IBC) comparable to microbiological biofilms. IBC protect bacteria from the immune system, are the cause of recurrent UTI and may cause symptoms, while standard urine culture does not indicate UTI. […] Depending on the risk factor, either the risk for bacteriuria, for cystitis and/or pyelonephritis is increased: HLA-A3, a low secretion of the Lewis blood group antigen via the urine, blood group antigen P1, expression of the globo-A epitope (AB0 blood group system) on epithelial cells, secretion of IgA via the vaginal mucus, defects of the TLR4 (toll-like receptor), low urine concentration of antimicrobial peptides.

• #89 (PDF) Urinary Tract Infection Pathogenesis

  https://www.academia.edu/16414163/Urinary_Tract_Infection_Pathogenesis

  Anatomic and functional problems of the urinary tract Although details of UTI among patients with anatomic and functional abnormalities of the urinary tract is included in the section on complicated UTIs, it is important to remember that these comorbid conditions defining complicated UTI also highlight key mechanical and functional host factors in the pathogenesis of UTI. […] Although gender is usually a nonmodifiable risk factor, the predilection of women for developing UTI can be used as a starting point for patient discussions of the pathogenesis of UTI, clinically relevant risk factors, and measures patients can take to reduce risk. […] Subsequently, findings in a large case-control study of healthy premenopausal women with and without a history of recurrent UTI showing that a history of first UTI before age 15 and a maternal history of UTI were associated with an increased risk of recurrent UTI suggested a genetic component.

• #90 The Pathogenesis of Urinary Tract Infections | IntechOpen

  https://www.intechopen.com/chapters/19318

  An understanding of pathogenic and anti-adherence mechanisms may allow physicians to develop appropriate strategies for UTI prevention and adequate management protocols. In the present chapter we discuss current concepts on the pathogenesis of UTIs with particular emphasis on pathogenic bacteria, virulence factors, predisposing factors, natural defences within genitourinary tract and consequences when these defence mechanisms are altered. […] Bacterial virulence factors play a significant role in determining whether an organism will invade the urinary tract and the level of infection acquired. Uropathogenic E. coli (UPEC) is present within bowel flora and pathogenic strains of this microorganism can infect the urinary tract by expressing specific virulence factors that permit adherence and colonisation of the lower urinary tract (Schlager et al. 2002, Yamamoto et al. 1997). Adherence of the micro-organism is dependent on 3 important environmental characteristics; firstly the bacterias own adhesive characteristics, secondly the receptive features of the urothelium and finally the fluid that is present between both surfaces (Schaeffer et al. 1981). Bacteria will migrate proximally and precipitate a host derived inflammatory response after adhering to the mucosal surface.

• #91 Antibiotic Resistant UTI | Treatments for Urinary Tract Infections

  https://www.antibioticresearch.org.uk/patient-support/specific-infections/urinary-tract-infections-utis/

  Antibiotic resistance occurs when the bacteria causing an infection either develop or acquire a mechanism that protects them against antibiotic treatments. […] Some strains of E. coli bacteria have begun to produce enzymes called extended-spectrum beta-lactamases (often summarised to ESBL E coli). These can make the bacteria resistant to certain antibiotics, and so the bacteria continue to multiply and spread. This causes more severe infection which becomes much more difficult to treat. […] The Enterobacteriaceae family can all cause UTIs and are often treated with the beta-lactam antibiotic, carbapenem, for which there are specific ESBL enzymes. The carbapenem resistant Enterobacteriaceae (CRE) that have developed, have become a real risk to health as the main antibiotic becomes useless and their presence increases in hospitals and care settings.

• #92 Antibiotic Resistant UTI | Treatments for Urinary Tract Infections

  https://www.antibioticresearch.org.uk/patient-support/specific-infections/urinary-tract-infections-utis/

  The main difference between a regular UTI and an antibiotic-resistant UTI is that the medicines usually used to treat such infections do not often work against antibiotic-resistant UTIs. […] The bacteria become harder to eradicate, even when taking powerful antibiotics, as they form a biofilm. This is where the colonies of resistant bacteria form a protective layer around themselves, making it even more difficult for antibiotics to reach and kill them. […] An antibiotic resistant UTI can then become a chronic condition and can often cause frequently recurring outbreaks of infection, with an increased risk of serious kidney infection (pyelonephritis) and even sepsis. […] If resistant organisms are discovered they are often found to be ESBL E. coli or ESBL Klebsiella. If you have a UTI with either of these resistant bacteria, you will probably be treated in hospital by an infectious disease doctor and their team. […] These are considered last resort antibiotics which are kept especially for those highly resistant bacterial infections.

• #93 Pathogenesis of Urinary Tract Infections | Encyclopedia MDPI

  https://encyclopedia.pub/entry/45913

  Bacteria also multiply as a result of biofilm protection, and if the infection is left untreated, it can progress to pyelonephritis and bacteremia. […] The spread of UTIs is closely linked to the effectiveness of a number of strategies that uropathogens have developed to adhere to and invade host tissues. […] Often, the infection does not seem particularly severe, especially in the early stages, but it can worsen significantly in the presence of complicating factors. […] Complicating factors that are involved in the progression of UTI are biofilms, urinary stasis due to obstruction, and catheters. […] The ability of different uropathogens to successfully adhere to and colonize the epithelium of the lower urinary tract is related to their ability to express specific virulence factors.

• #94 Urinary Tract Infections: The Current Scenario and Future Prospects

  https://www.mdpi.com/2076-0817/12/4/623

  Urinary tract infections (UTIs) begin when gut-resident uropathogens colonize the urethra and subsequently the bladder through the action of specific adhesins. […] If the host’s inflammatory response fails to eliminate all bacteria, they begin to multiply, producing toxins and enzymes that promote their survival. […] Subsequent colonization of the kidneys can evolve into bacteremia if the pathogen crosses the kidney epithelial barrier. […] In complicated UTIs, infection by uropathogens is followed by bladder compromise, which occurs with catheterization. […] Uropathogens, through the expression of fibrinogen-binding proteins, bind to the catheter. […] Bacteria also multiply as a result of biofilm protection, and if the infection is left untreated, it can progress to pyelonephritis and bacteremia.

• #95 Urinary Tract Infections Caused by Uropathogenic Escherichia coli: Mechanisms of Infection and Treatment Options

  https://www.mdpi.com/1422-0067/24/13/10537

  The fifth step is invasion and replication via the formation of IBCs in the bladder, where quiescent intracellular reservoirs (QIRs) arise in the underlying urothelium. Bacterial replication in these IBCs can easily reach as high as 10^5 bacteria per cell. Additionally, bacteria in the IBCs undergo morphological changes, emerge from the infected cell, and enter neighboring cells, which spreads the infection. The sixth step is kidney colonization. UPEC destroy host tissues by releasing toxins, causing upper UTIs, and severe cases may lead to dangerous conditions, including bacteremia, septicemia, urosepsis, and even death. […] In general, the strategies of pathogenesis employed by UPEC include adherence, motility, the acquisition of metals, toxin production, and immune evasion. The bacterial adhesins and their receptors on the host’s cells mediate the processes of bacterial colonization, biofilm formation, replication, secretion of toxins, internalization, and invasion.

• #96 Bacterial Urinary Tract Infections – Genitourinary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/genitourinary-disorders/urinary-tract-infections-utis/bacterial-urinary-tract-infections

  The urinary tract, from the kidneys to the urethral meatus, is normally sterile and resistant to bacterial colonization despite frequent contamination of the distal urethra with colonic bacteria. The major defense against urinary tract infection (UTI) is complete emptying of the bladder during urination. Other mechanisms that maintain the tracts sterility include urine acidity, the vesicoureteral valve, and various immunologic and mucosal barriers. […] About 95% of UTIs occur when bacteria ascend the urethra to the bladder and, in the case of pyelonephritis, ascend the ureter to the kidney. The remainder of UTIs are hematogenous. Systemic infection can result from UTI, particularly in older patients. Urinary tract infections are a common cause of hospital-acquired bacteremia. […] Pyelonephritis is bacterial infection of the kidney parenchyma. The term should not be used to describe tubulointerstitial nephropathy unless infection is documented. In women, pyelonephritis is a common cause of community-acquired bacteremias. Pyelonephritis is uncommon in men with a normal urinary tract.

• #97 Urinary Tract Infections Caused by Uropathogenic Escherichia coli: Mechanisms of Infection and Treatment Options

  https://www.mdpi.com/1422-0067/24/13/10537

  The fifth step is invasion and replication via the formation of IBCs in the bladder, where quiescent intracellular reservoirs (QIRs) arise in the underlying urothelium. Bacterial replication in these IBCs can easily reach as high as 10^5 bacteria per cell. Additionally, bacteria in the IBCs undergo morphological changes, emerge from the infected cell, and enter neighboring cells, which spreads the infection. The sixth step is kidney colonization. UPEC destroy host tissues by releasing toxins, causing upper UTIs, and severe cases may lead to dangerous conditions, including bacteremia, septicemia, urosepsis, and even death. […] In general, the strategies of pathogenesis employed by UPEC include adherence, motility, the acquisition of metals, toxin production, and immune evasion. The bacterial adhesins and their receptors on the host’s cells mediate the processes of bacterial colonization, biofilm formation, replication, secretion of toxins, internalization, and invasion.

• #98 Urinary Tract Infection: Pathogenesis and Outlook

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5159206/

  Some of these bacteria will go on to infect immature bladder epithelium which is exposed after exfoliation, later forming quiescent intracellular reservoirs, which avoid immune clearance and resist systemic antibiotic treatment. […] These persistent UPEC may re-emerge, in response to currently undefined signals, to cause the recurrent cystitis that is so clinically common. […] A significant gap in our understanding is the mechanism by which UPEC escape the initial vacuole (after internalization) to reach the cytoplasm, where the IBC is formed. […] Following escape into the cytoplasm, the bacteria find themselves occupying an environment very different from the nutrient-poor bladder lumen. […] Transcriptomic analyses of UPEC in different models have suggested that various metabolic pathways are essential for pathogenesis; these include sialic acid transport/metabolism, gluconeogenesis, the tricarboxylic acid (TCA) cycle, iron uptake, ethanolamine and phosphate metabolism, as well as amino acid metabolism.

• #99 Research : WUSTL Hultgren Lab

  https://hultgrenlab.wustl.edu/research/urinary-tract-infection/

  Understanding how prior infection influences a new infection is needed in order to understand clinical recurrent UTI. […] Thus, although it has long been known that a history of UTIs is the greatest independent risk factor for the development of a UTI, our recent studies elucidating the long-term consequences to the bladder tissue have shown that an initial chronic cystitis can remodel the bladder tissue, thus making it more susceptible for recurrent infections even with less virulent pathogens. […] UPEC commonly exists as a minor member of the gut microbiota, establishing a reservoir in the gastrointestinal tract (GIT) from which UPEC can then be shed in the feces and colonize the periurethral area or vagina. UPEC can subsequently ascend through the urethra to the urinary tract (UT) to cause infection.

• #100 Urinary Tract Infection – Pathophysiology – Presentation – TeachMePaeds

  https://teachmepaediatrics.com/nephrology/post-renal/urinary-tract-infection/

  All infants with an unexplained temperature of 38oC or more should have their urine sent for microscopy and culture within 24 hours. […] If a UTI is suspected then perform a urine dipstick. If leukocyte esterase and nitrites are positive then send the urine sample for microscopy and culture. […] All infants younger than 3 months with a suspected UTI should be referred immediately to the care of a paediatric specialist for urine analysis and treatment with parenteral antibiotics. […] Antibiotic prophylaxis may be considered in infants or children with recurrent UTI. However, this is normally prescribed by a specialist. […] Possible complications of UTIs in children are: Renal scarring/damage renal scarring is almost always preceded by an upper UTI however not all upper UTIs go on to cause renal scarring, Hypertension may be associated with UTI in childhood but risk is small unless the child has severe renal scarring, There is a possible link with bacteriuria and hypertension in pregnancy a few studies suggest that pregnant women with a history of childhood UTI are at an increased risk of bacteriuria, hypertension (if renal scarring present) and pre-eclampsia, Renal insufficiency and failure there is an increased risk for established renal failure and chronic renal failure in patients with febrile UTI that is treated late.

• #101 Pathophysiology of an UTI | Urinary Tract Infection Case Study

  https://u.osu.edu/utieducation/pathophysiology-of-uti/

  The inflammation and hardening of the wall of the bladder can also create hemorrhagic ulcers and a decrease in bladder capacity. The epithelial cells of the bladder also secrete antiproliferative factor (AFP) which block cell growth of the inner wall of the bladder and causes an increased bladder sensation (McCance Huether, 2019). […] Pyelonephritis is an infection of one or both upper urinary tracts. Acute pyelonephritis is usually associated with the microorganisms E. coli, Proteus, and Pseudomonas. Urinary obstruction and reflux of urine from the bladder are the most common risk factors, along with being a female. […] Chronic pyelonephritis is recurrent infection of the kidney which leads to scarring. Various causes are idiopathic, chronic UTIs, renal stones, or recurrent episodes of acute pyelonephritis. Chronic UTIs prevent the elimination of bacteria and triggers the inflammatory process which leads to destruction or atrophy of the tubules, significant scarring and impaired urine concentrating ability. These all ultimately lead to chronic kidney failure (McCance Huether, 2019).

• #102 Urinary tract infections: epidemiology, mechanisms of infection and treatment options

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4457377/

  UPEC also secretes cytotoxic necrotizing factor 1 (CNF1), which affects actin remodelling in the host cell through three small RHO GTPases: RAC1, RHOA and cell division control 42 (CDC42). […] The expression of all of these virulence factors is regulated by the quorum sensing system. […] Urease is encoded by several uropathogens, including P. mirabilis, S. saprophyticus, K. pneumoniae and P. aeruginosa, and is important for colonization and persistence during P. mirabilis and S. saprophyticus UTIs. […] The high activity level of the P. mirabilis enzyme induces rapid crystal formation, and these crystals become trapped within the polysaccharides produced by attached bacterial cells, forming crystalline biofilms on catheters. […] These structures also block urine drainage from the ureters, potentially resulting in reflux and promoting progression to pyelonephritis, septicaemia and shock.

• #103 Urinary Tract Infections During Pregnancy | AAFP

  https://www.aafp.org/pubs/afp/issues/2000/0201/p713.html

  Acute pyelonephritis during pregnancy is a serious systemic illness that can progress to maternal sepsis, preterm labor and premature delivery. […] Early, aggressive treatment is important in preventing complications from pyelonephritis. […] The majority of UTIs are caused by gastrointestinal organisms. Even with appropriate treatment, the patient may experience a reinfection of the urinary tract from the rectal reservoir. […] A postpartum urologic evaluation may be necessary in patients with recurrent infections because they are more likely to have structural abnormalities of the renal system. […] The maternal and neonatal complications of a UTI during pregnancy can be devastating. Thirty percent of patients with untreated asymptomatic bacteriuria develop symptomatic cystitis and up to 50 percent develop pyelonephritis. […] While this does not prove a cause and effect relationship, randomized trials have demonstrated that antibiotic treatment decreases the incidence of preterm birth and low-birth-weight infants.

• #104 Urinary Tract Infection: Pathogenesis and Outlook

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5159206/

  UPEC can subvert and delay the innate immune response in multiple ways. […] While robust innate defenses are able to repel most bacterial challenges, this inflammatory response may represent a double-edged sword. […] Understanding the basis of functional adaptive immunity against UTI could have major implications for recurrent UTIs and vaccine development. […] Contemporary development of novel UTI therapeutics has focused on interfering with pathogen binding to bladder epithelium or other key pathogen processes, the development of vaccines based on bacterial components, as well as the modulation of host responses. […] Successful vaccination against UPEC and other uropathogens could have monumental impact on the lives of those at risk for complicated UTIs or who suffer from recurring episodes. […] Advanced, more efficacious exfoliants are being designed to unearth these quiescent reservoirs. […] As the urinary microbiome is more extensively defined, we will have to account for it when considering the pathogenesis of UTI, as well as when choosing therapies for symptomatic patients.

• #105 Call for papers – Urinary tract infections

  https://www.biomedcentral.com/collections/uti

  BMC Infectious Diseases is welcoming submissions to our Collection on Urinary tract infections (UTIs), dedicated to advancing our understanding of the pathogenesis, diagnosis, treatment, and prevention of UTIs. […] A current major focus of the De Nisco Lab is defining the metabolic relationships between the urinary microbiota and the human host in health and disease. […] This Collection seeks to address these challenges by highlighting advancements in our understanding and management of UTIs. […] Pathogenesis and microbiology: investigations into the molecular mechanisms of Uropathogenic Escherichia coli, Staphylococcus saprophyticus, Klebsiella spp., Pseudomonas spp., Candida albicans, Enterococcus spp., and Staphylococcus aureus. […] Uropathogenic Escherichia coli (UPEC) is the predominant cause of urinary tract infections (UTIs), and the recurrence of these infections poses significant treatment challenges.

• #106 Urinary Tract Infection (UTI) Vaccine and Treatment — Vax-Before-Travel

  https://www.vax-before-travel.com/urinary-tract-infection-uti-vaccine-and-treatment

  Urinary tract infections (UTIs) are among the most common bacterial infections, affecting hundreds of millions of women and men annually. Most UTIs are caused by uropathogenic E. coli (E. coli). Less common pathogens, such as Enterococcus faecalis and other enterococci, cause infections by infecting an abnormal or catheterized urinary tract. […] A mini-review published in January 2025 summarizes the existing state of UTI diagnostics and covers current and upcoming technologies, including rapid molecular-based pathogen identification, next-generation sequencing, and advanced antimicrobial susceptibility testing. However, these methods represent unique challenges, and as they are implemented, they will require the field to adapt to new concepts to avoid misdiagnosis and overtreatment. […] A Research Article published in March 2021 – Local induction of bladder Th1 responses to combat urinary tract infections – concluded that intravesical vaccination with one or more UPEC antigens to induce bladder Th1 responses represents a superior strategy to combat UTIs, especially in UTI-prone subjects.

• #107 Role of D-mannose in urinary tract infections – a narrative review | Nutrition Journal | Full Text

  https://nutritionj.biomedcentral.com/articles/10.1186/s12937-022-00769-x

  Urinary tract infections (UTIs) are one of the most prevalent bacterial diseases worldwide. […] D-mannose, a monosaccharide naturally found in fruits, is commonly marketed as a dietary supplement for reducing the risk for UTIs. […] When excreted in urine, D-mannose potentially inhibits Escherichia coli, the main causative organism of UTIs, from attaching to urothelium and causing infection. […] The adhesion of E. coli in the urinary tract is mainly based on mannose-sensitive mechanism, where E. coli type I pili adhere to mannose structures on the uroepithelial cell surfaces. […] Research suggests that free D-mannose in urine has the potential to saturate E. coli FimH structures, and subsequently block E. coli adhesion to urinary tract epithelial cells. This so-called competitive inhibition is considered as one of the potential mechanisms for preventing UTI development.

• #108 Role of D-mannose in urinary tract infections – a narrative review | Nutrition Journal | Full Text

  https://nutritionj.biomedcentral.com/articles/10.1186/s12937-022-00769-x

  Furthermore, this can potentially lead to more severe infection or risk for recurrence as the pathogen might remain hidden inside the uroepithelial cells. […] The affinity between FimH and mannosides shown in vitro and animal models will presumably prevent the bacterial entry and infection of the urinary tract cells and thus provide therapeutic value and scientific rationale for mannose supplementation as a prophylactic treatment for UTIs in humans.

• #109 Deep insights into urinary tract infections and effective natural remedies | African Journal of Urology | Full Text

  https://afju.springeropen.com/articles/10.1186/s12301-020-00111-z

  Probiotics are living microorganisms which when administered in certain numbers exert a health benefit on the host. The clinical efficacy of probiotics for adjunct treatment in the treatment of different gastrointestinal and urinary tract infections has been addressed previously. They have demonstrated positive effects in the treatment and prevention of rotavirus diarrhea and alleviation of the antibiotic-associated intestinal adverse effects by recognizing the commensal microbiota and also restoration of the microbial ecosystem after an imbalance or infection. Probiotics are clinically proven to be effective in the management of UTI including accelerating recovery after UTI and also decreasing recurrent UTI in children.

• #110 Urinary Tract Infection (UTI) Vaccine and Treatment — Vax-Before-Travel

  https://www.vax-before-travel.com/urinary-tract-infection-uti-vaccine-and-treatment

  In various clinical trials, Locus Biosciences is developing LBP-EC01, a CRISPR-enhanced bacteriophage therapy for treating UTIs and other infections caused by the pathogen E. coli. It is a bacteriophage cocktail engineered with a CRISPR-Cas3 construct targeting the E. coli gene. It is not a broad-spectrum antibacterial that kills various bacterial species. The precision medicine product works through a unique dual mechanism of action, utilizing both the natural lytic activity of the bacteriophage and the DNA-targeting activity of CRISPR-Cas3.

• #111 A novel home-use culture mechanism for identifying microbial load in urine samples | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0285881

  Diagnosing a urinary tract infection (UTI) is typically a clinical procedure involving multiple steps. […] Given the current pandemic situation, visiting a clinic may not be a preferable choice for many users. […] So far, microbial cultures have been used as the gold standard for the diagnosis of an infection. […] Therefore, there is a need for a home-use culture kit that can serve this purpose. […] UTI is acquired by up to 5060% of individuals at least once in their lifetime. […] If undiagnosed, UTI can complicate to a renal infection and therefore individuals at risk need to undergo regular screening to avoid further complications or progression to complicated UTIs. […] A common method of diagnosing UTI is using urinalysis dipsticks. […] However, these tests provide inaccurate results nearly 33% of the time, and their sensitivity ranges from 2395.6%, depending on the type of patient.

• #112 A novel home-use culture mechanism for identifying microbial load in urine samples | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0285881

  For these reasons, urine culture is considered the gold standard for diagnosing UTIs. […] However, the traditional way of performing a microbial culture requires skilled technicians and considerable time (around 48 hours) for results to reach the patient. […] Therefore, there is a need for an easy-to-use home based culturing mechanism which is user-friendly as well as accurate enough to be used by physicians. […] This study presents a novel home-based method for culturing and detecting microbes. […] Our primary goal was to design a system derived from the dipstick format and integrate it with a culture medium, which can also be extended to other cultures and infections. […] We also found that the setup conceived through this work could be used to deliver urine samples to the culture media without the need of pipetting it on the media and spreading it making it a more user-friendly and less technically challenging workflow.

• #113 Pathogenesis of Urinary Tract Infections | Encyclopedia MDPI

  https://encyclopedia.pub/entry/45913

  Uropathogenic E. coli (UPEC) is the most common causative agent of both uUTIs and cUTIs. […] On the cell surface of uropathogens are several adhesion proteins that play a crucial role in the initial interactions between the host and pathogen. […] In addition, adhesins have recently been found to promote both the attachment of bacteria and invasion of host tissues in the urinary tract. […] Biofilm formation by these pathogenic bacteria requires specific virulence factors that play a key role in inducing adhesion to host epithelial cells or catheter materials. […] Bacterial biofilms play an important role in UTIs, being responsible for the persistence of infections that result in recurrence and relapse. […] Since eradication of biofilms often cannot be achieved by antibiotic treatment, new approaches for eradication of aggressive biofilms are being tested, such as phagotherapy, enzymatic degradation, antimicrobic peptides, and nanoparticles.

• #114 Research : WUSTL Hultgren Lab

  https://hultgrenlab.wustl.edu/research/urinary-tract-infection/

  Understanding how prior infection influences a new infection is needed in order to understand clinical recurrent UTI. […] Thus, although it has long been known that a history of UTIs is the greatest independent risk factor for the development of a UTI, our recent studies elucidating the long-term consequences to the bladder tissue have shown that an initial chronic cystitis can remodel the bladder tissue, thus making it more susceptible for recurrent infections even with less virulent pathogens. […] UPEC commonly exists as a minor member of the gut microbiota, establishing a reservoir in the gastrointestinal tract (GIT) from which UPEC can then be shed in the feces and colonize the periurethral area or vagina. UPEC can subsequently ascend through the urethra to the urinary tract (UT) to cause infection.

• #115 Research : WUSTL Hultgren Lab

  https://hultgrenlab.wustl.edu/research/urinary-tract-infection/

  Despite appropriate antibiotic treatment, more than 60% of recurrent UTIs (rUTIS) are due to the same strain of E. coli that caused the initial infection, consistent with re-inoculation of the UT from a persistent GIT reservoir. […] UPEC persistence within the human gut microbiota is an important susceptibility factor for rUTI.

• #116 Urinary Tract Infection: Pathogenesis and Outlook

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5159206/

  Upon reaching the urinary bladder, UPEC bind to superficial epithelial (facet) cells in a type 1 pili-dependent manner. […] A subset of adherent bacteria are then internalized into facet cells, a dynamic process that likely relies on the normal cycling of apical membrane segments in these cells. […] Recent data show that UPEC are capable of neutralizing the lysosome, and that this neutralization is sensed by a lysosomal membrane protein termed mucolipin TRP channel 3 (TRPML3), activating pathways that direct exocytosis of UPEC-containing lysosomes. […] Using incompletely defined strategies, UPEC may gain access to the bladder epithelial cell cytoplasm, thereafter developing clonal, biofilm-like masses termed intracellular bacterial communities (IBCs). […] After 16-24 h in murine UTI models, a subset of UPEC in remaining IBCs adopt a neutrophil-resistant, filamentous morphology and escape the IBCs, subsequently re-invading nave bladder epithelial cells.

• #117 Urinary Tract Infections Caused by Uropathogenic Escherichia coli: Mechanisms of Infection and Treatment Options

  https://www.mdpi.com/1422-0067/24/13/10537

  The fifth step is invasion and replication via the formation of IBCs in the bladder, where quiescent intracellular reservoirs (QIRs) arise in the underlying urothelium. Bacterial replication in these IBCs can easily reach as high as 10^5 bacteria per cell. Additionally, bacteria in the IBCs undergo morphological changes, emerge from the infected cell, and enter neighboring cells, which spreads the infection. The sixth step is kidney colonization. UPEC destroy host tissues by releasing toxins, causing upper UTIs, and severe cases may lead to dangerous conditions, including bacteremia, septicemia, urosepsis, and even death. […] In general, the strategies of pathogenesis employed by UPEC include adherence, motility, the acquisition of metals, toxin production, and immune evasion. The bacterial adhesins and their receptors on the host’s cells mediate the processes of bacterial colonization, biofilm formation, replication, secretion of toxins, internalization, and invasion.

• #118 :: Immune Network ::

  https://www.immunenetwork.org/DOIx.php?id=10.4110/in.2024.24.e31

  Urinary tract infections (UTIs) represent one of the most prevalent bacterial infections globally, manifesting in diverse clinical phenotypes with varying degrees of severity and complications. The mechanisms underlying UTIs are gradually being elucidated, leading to an enhanced understanding of the immune responses involved. Innate immune cells play a crucial defensive role against uropathogenic bacteria through various mechanisms. […] Despite their significant contributions to host defense, these cells often fail to achieve complete clearance of uropathogens, necessitating the frequent prescription of antibiotics for UTI patients. However, the persistence of infections and related pathological symptoms in the absence of innate immune cells in animal models underscore the importance of innate immunity in UTIs. Therefore, the host protective functions of innate immune cells, including neutrophils, macrophages, mast cells, NK cells, innate lymphoid cells, and T cells, are delicately coordinated and timely regulated by a variety of cytokines to ensure successful pathogen clearance.

• #119 Urinary Tract Infection: Pathogenesis and Outlook

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5159206/

  UPEC can subvert and delay the innate immune response in multiple ways. […] While robust innate defenses are able to repel most bacterial challenges, this inflammatory response may represent a double-edged sword. […] Understanding the basis of functional adaptive immunity against UTI could have major implications for recurrent UTIs and vaccine development. […] Contemporary development of novel UTI therapeutics has focused on interfering with pathogen binding to bladder epithelium or other key pathogen processes, the development of vaccines based on bacterial components, as well as the modulation of host responses. […] Successful vaccination against UPEC and other uropathogens could have monumental impact on the lives of those at risk for complicated UTIs or who suffer from recurring episodes. […] Advanced, more efficacious exfoliants are being designed to unearth these quiescent reservoirs. […] As the urinary microbiome is more extensively defined, we will have to account for it when considering the pathogenesis of UTI, as well as when choosing therapies for symptomatic patients.

• #120 Urinary tract infections: epidemiology, mechanisms of infection and treatment options | Nature Reviews Microbiology

  https://www.nature.com/articles/nrmicro3432

  Urinary tract infections (UTIs) are some of the most common bacterial infections and are caused by both Gram-negative and Gram-positive species. UTIs are categorized into uncomplicated and complicated, and are a severe public health problem; this situation is being exacerbated by the rise in multidrug-resistant strains. […] Uropathogens carry multiple virulence factors involved in the pathophysiology of UTIs. These virulence factors are involved in invasion and colonization, as well as in mediating the subversion of host defences. […] Knowledge about the mechanism of action of these virulence factors is being used to develop new therapeutics against UTIs. […] Therapies that are currently in the initial stages of development include vaccines targeting bacterial factors that are essential for initial attachment and disease progression (such as adhesins, toxins, proteases and siderophores), and small-molecule inhibitors that prevent adhesin-receptor interactions. […] In this Review, we discuss how basic science studies are elucidating the molecular details of the crosstalk that occurs at the host-pathogen interface, as well as the consequences of these interactions for the pathophysiology of UTIs.

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