Materiały źródłowe

• #1

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4886739/

  Chlamydia spp. are important causes of human disease for which no effective vaccine exists. These obligate intracellular pathogens replicate in a specialized membrane compartment and use a large arsenal of secreted effectors to survive in the hostile intracellular environment of the host. […] The binding of elementary bodies to host cells is initiated by the formation of a trimolecular bridge between bacterial adhesins, host receptors and host heparan sulfate proteoglycans (HSPGs). Next, pre-synthesized type III secretion system (T3SS) effectors are injected into the host cell, some of which initiate cytoskeletal rearrangements to facilitate internalization and/or initiate mitogenic signalling to establish an anti-apoptotic state. […] Chlamydiae have substantially reduced genomes (1.04 Mb encoding 895 open reading frames for C. trachomatis) that lack many metabolic enzymes, which makes these bacteria reliant on the host for many of their metabolic requirements.

• #1

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4886739/

  Chlamydia spp. use the T3SS at various stages of infection, including during initial host cell contact with the plasma membrane and during the intracellular phase, in which effectors are injected into the cytosol of the host cell and can access other intracellular compartments, such as the nucleus. […] The intracellular survival of Chlamydia spp. depends on the ability of the inclusion to inhibit fusion with some compartments (for example, with lysosomes) while promoting fusion with others (for example, with nutrient-rich exocytic vesicles). […] Chlamydia spp. scavenge nutrients from various sources, for example, from the lysosomal-mediated degradation of proteins, using various transporters. […] Chlamydia spp. activate pro-survival pathways and inhibit apoptotic pathways. […] Chlamydia spp. can block intrinsic apoptosis through numerous mechanisms including the MDM2-mediated ubiquitylation and proteasomal degradation of the tumour suppressor p53, the sequestration of pro-apoptotic protein kinase C (PKC) or BCL-2-associated agonist of cell death (BAD) to the inclusion membrane through diacylglycerol or 14-3-3-binding Incs, respectively, and the upregulation or stabilization of anti-apoptotic proteins including BAG family molecular chaperone regulator 1 (BAG1), myeloid leukaemia cell differentiation protein 1 (MCL1) or cIAP2. […] Chlamydia spp. cause substantial changes in gene expression and protein production in the host, at the transcriptional, translational and post-translational levels.

• #2 Chlamydia cell biology and pathogenesis | Nature Reviews Microbiology

  https://www.nature.com/articles/nrmicro.2016.30

  Chlamydiae spp. are obligate intracellular pathogens that are important causes of human and animal diseases. Chlamydiae share a common developmental cycle in which they alternate between the extracellular, infectious elementary body and the intracellular, non-infectious reticulate body. […] Chlamydiae use several redundant mechanisms to enter host cells and to establish their intracellular membrane bound niche the inclusion. […] Chlamydiae deliver effector proteins into the inclusion membrane and into host cells to promote replication and survival. […] Chlamydiae encode a unique set of T3SS effectors, the inclusion membrane proteins (Incs), which are inserted into the inclusion membrane where they may function as structural determinants of the membrane or as scaffolds to interface with various cell pathways in the host.

• #3 Chlamydia (Chlamydial Genitourinary Infections): Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/214823-overview

  Chlamydiae have a unique biphasic life cycle that is adaptable to both intracellular and extracellular environments. In the extracellular milieu, the so-called elementary body (EB) is found. EBs are metabolically inactive infectious particles; functionally, they are spore-type structures. Once inside a susceptible host cell, the EB prevents phagosome-lysozyme fusion and then undergoes reorganization to form a reticulate body (RB). […] The RB synthesizes its own DNA, RNA, and proteins but requires energy in the form of adenosine triphosphate (ATP) from the host cell. After a sufficient amount of RBs have formed, some transform back into EBs, exiting the cell to infect others. […] The bacterium usually is spread through sexual activity. An infected male has a 25% chance per sexual encounter of transmitting the infection to an uninfected female. Chlamydiae can be vertically spread as well. The transmission rate from infected mother to newborn is 50-60%, causing conjunctivitis (in most cases) or pneumonia (in 10-20% of cases; see Afebrile Pneumonia Syndrome).

• #3 Chlamydia (Chlamydial Genitourinary Infections): Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/214823-overview

  Chlamydia infects columnar epithelial cells, which places the adolescent female at particular risk because of the presence of the squamocolumnar junction on the ectocervix until early adulthood. […] The initial response of epithelial cells to infection is a neutrophilic infiltration, followed by lymphocytes, macrophages, plasma cells, and eosinophilic invasion. The release of cytokines and interferons by the infected epithelial cell initializes this inflammatory cascade. […] Infection with chlamydial organisms invokes a humoral cell response, resulting in secretory immunoglobulin A (IgA) and circulatory immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies and a cellular immune response. A 40-kd major outer membrane protein (MOMP) and 10- and 60-kd chlamydial heat-shock proteins (cHSPs) have been implicated in the immunopathologic response, but further studies are needed to provide a better understanding of these cell-mediated immune responses.

• #3 Chlamydia (Chlamydial Genitourinary Infections): Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/214823-overview

  Infection of the genital tract is the most common clinical presentation. The incubation period is 1-3 weeks. Approximately 50% of infected males and 80% of infected females are asymptomatic, but infection may cause a mucopurulent cervicitis in females and urethritis in males. Ascending infection can result in PID in women and is the most common cause of epididymitis in men younger than 35 years. Of women with PID, 5-10% develop perihepatitis (ie, Fitz-Hugh-Curtis syndrome). […] Although patients with any STD are at increased risk of coinfection with another STD, coinfection of chlamydia and gonorrhea is most common. Forty percent of women and 20% of men with chlamydial infection are co-infected with gonorrhea. Patients with chlamydia also have a higher frequency of Reiter syndrome (ie, urethritis, conjunctivitis, reactive arthritis) than the general population.

• #4 VFDB – pathogenesis of Chlamydia

  https://www.mgc.ac.cn/cgi-bin/VFs/genus.cgi?Genus=Chlamydia

  General information: Gram-negative-type cell wall but no peptidoglycan. Smaller than most bacteria. Constitute an important group of pathogens responsible for acute and chronic diseases of humans and are also of veterinary importance. C. trachomatis and C. pneumoniae are the primary species pathogenic for humans. […] Like Salmonella and Shigella, chlamydiae use the activity of small GTPases of the Rho family to transiently remodel the actin cytoskeleton and invade eukaryotic cells. All species share a unique developmental cycle during multiplication in a vacuole, called an inclusion, within a host cell. The infectious form of the developmental cycle, called the elementary body (EB), is small (about 0.3μm in diameter) and essentially metabolically inactive. After entering epithelial host cells, EBs differentiate within a few hours into larger (about 1μm), more pleomorphic, reticulate bodies (RBs). RBs are metabolically active, noninfectious, and represent the replicating form.

• #4 VFDB – pathogenesis of Chlamydia

  https://www.mgc.ac.cn/cgi-bin/VFs/genus.cgi?Genus=Chlamydia

  Major virulence factors in Chlamydia: Adherence MOMP (Major outer membrane protein) OmcB (Outer membrane complex protein B) Pmps (Polymorphic membrane proteins) […] Invasion Ctad1 (C. trachomatis adhesin 1) […] Effector delivery system TTSS (Type III secretion system) TTSS secreted effectors […] Exoenzyme CPAF (Chlamydial protease-like activating factor)

• #5 Insights into Chlamydia Development and Host Cells Response

  https://www.mdpi.com/2076-2607/12/7/1302

  Chlamydia infections commonly afflict both humans and animals, resulting in significant morbidity and imposing a substantial socioeconomic burden worldwide. As an obligate intracellular pathogen, Chlamydia interacts with other cell organelles to obtain necessary nutrients and establishes an intracellular niche for the development of a biphasic intracellular cycle. Eventually, the host cells undergo lysis or extrusion, releasing infectious elementary bodies and facilitating the spread of infection. […] Chlamydia, as Gram-negative obligate intracellular bacteria, rely on host-derived nutrients to support their growth, development, reproduction, and successful infection while concurrently modulating the metabolic mechanisms and physiological processes of host cells. […] The Chlamydiaceae family undergoes a characteristic biphasic developmental cycle, including a crucial morphological transition from elementary bodies (EBs) to reticulate bodies (RBs) upon entering the host cells for propagation, and then differentiating back into EBs to generate infectious progeny.

• #5 Insights into Chlamydia Development and Host Cells Response

  https://www.mdpi.com/2076-2607/12/7/1302

  The effective adhesion to host cells plays a crucial role in the invasion and survival of Chlamydia. […] The attachment of Chlamydia involves two steps: low-affinity electrostatic interaction with heparin sulfate proteoglycan (HSPGs) and then high-affinity binding to host cell receptors. […] The release of EBs from host cells is achieved through two mutually exclusive mechanisms: either by cell lysis, which is triggered by the activation of cysteine proteases, or by extrusion of Chlamydia vacuoles or liberation of Chlamydia within cytoplasmic fragments enclosed by cell membranes. […] The acquisition of essential nutrients by Chlamydia inclusions involves selective redirection of transport vesicles and hijacking of intracellular organelles. […] Chlamydia spp. lack necessary biosynthetic enzymes and even entire metabolic pathways; thus, they rely on host cells to absorb nutrients for their own growth and reproduction.

• #5 Insights into Chlamydia Development and Host Cells Response

  https://www.mdpi.com/2076-2607/12/7/1302

  The death of host cells has long been considered the ultimate phase in the Chlamydia infection cycle, and the manner in which EBs are released affects the degree of tissue damage and inflammation at the site of infection. These factors subsequently affect the potency of the immune response, ultimately regulating the survival and transmission potential of Chlamydia. […] The Chlamydia genome not only contains genes associated with crucial enzymes in aerobic respiration, but also harbors protein-coding genes resembling virulence factors found in other bacteria. […] The Chlamydia transporter contains a highly developed and complete Type III secretion system (T3SS), which is universally present in Chlamydiae for acquiring indispensable nutrients from the host cell and evading its innate defense mechanisms.

• #6 Chlamydia – Clinical Features – Management – TeachMeObGyn

  https://teachmeobgyn.com/sexual-health/sexually-transmitted-infections/chlamydia/

  C. trachomatis is an obligate intracellular gram negative bacterium of which there are different serotypes: […] C. trachomatis enters the host cell as an elementary body (infectious form). Once inside the cell it becomes a reticular body, the non-infectious form capable of replication. Following replication, these reticular bodies mature back to elementary bodies, and following cell rupture the elementary bodies infect other cells resulting in inflammation and tissue damage.

• #7 Core Concepts – Chlamydial Infections – Self-Study Lessons – National STD Curriculum

  https://www.std.uw.edu/go/comprehensive-study/chlamydial-infections/core-concept/all

  Chlamydia trachomatis infects columnar epithelial cells at mucosal sites, often becoming a chronic infection that may last months or even longer than a year if untreated. Chlamydia trachomatis has a complex replicative cycle, typically requiring 48 to 72 hours to complete. The organisms replicate within a host cell, frequently causing eventual death of the host cell. The life cycle of C. trachomatis involves five key steps: The elementary body, a small, infectious, but nonreplicating particle found in secretions, attaches to and enters a host cell, such as an endocervical or urethral columnar epithelial cell. The contact with the host cell membrane causes the elementary body to induce its own endocytosis. Within 8 hours, the now-intracellular elementary body interacts with glycogen and transforms into a reticulate body, which begins to multiply within an isolated intracellular structure referred to as an inclusion. The reticulate bodies are the noninfectious replicating form. Within 48 hours, some reticulate bodies begin to reorganize back to elementary bodies. Within 72 hours, most of the reticulate bodies have transitioned back to elementary bodies, and the inclusion either undergoes lysis at the host cell wall or the intact inclusion (containing numerous elementary bodies) is released into the extracellular space, a process called extrusion. Regardless of whether the inclusion undergoes lysis or extrusion, the elementary bodies are released to infect adjacent cells or to be transmitted to and infect another person.

• #7 Core Concepts – Chlamydial Infections – Self-Study Lessons – National STD Curriculum

  https://www.std.uw.edu/go/comprehensive-study/chlamydial-infections/core-concept/all

  Chlamydia trachomatis is an obligate intracellular bacterium with a cell wall and ribosomes similar to those of gram-negative organisms. The C. trachomatis cell wall is unique in that it contains an outer lipopolysaccharide membrane, but it lacks peptidoglycan; within the cell wall, cysteine-rich proteins act as the functional peptidoglycan equivalent. The absence of peptidoglycan explains why the organism is not seen with a standard Gram stain. Chlamydia trachomatis is a member of the Chlamydiaceae family. The genus Chlamydia includes three species that infect humans: C. trachomatis, C. pneumoniae, and C. psittaci. […] The species C. trachomatis, which exclusively infects humans, can cause distinct infections in different populations, including (1) trachoma in persons of all ages, (2) anogenital infections, lymphogranuloma venereum (LGV), and conjunctivitis in adolescents and adults, and (3) conjunctivitis and pneumonia in neonates. The type of clinical infection caused by C. trachomatis is determined by the outer membrane protein A (OmpAalso known as the major outer membrane protein [MOMP]), which can be determined based on serology (OmpA serovar) or molecular methods (OmpA genotype). These techniques are not routinely used for clinical purposes. Genital, rectal, oropharyngeal, and conjunctival infections are usually caused by C. trachomatis serovars D through K (as is conjunctivitis and pneumonia in neonates), chronic keratoconjunctivitis (trachoma) by serovars A through C, and lymphogranuloma venereum (LGV) by serovars L1, L2, or L3.

• #8 Chlamydia – Medical Microbiology – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK8091/

  Chlamydiae have a hemagglutinin that may facilitate attachment to cells. The cell-mediated immune response is largely responsible for tissue damage during inflammation, although an endotoxin-like toxin has been described. […] Chlamydial agents are intracytoplasmic obligate parasites of mammalian cells and can damage infected cells in tissues. The elementary bodies are infectious particles that can be transmitted from the infected tissues to uninfected tissues in the same person (transfer of C trachomatis elementary bodies from an infected genital tract to the eyes and vice versa) or from a person with atypical pneumonia (caused by C psittaci or C pneumoniae) to healthy individuals (respiratory release of elementary bodies). In the infected individuals the chlamydial agent causes tissue damage and induction of interleukin-1, interleukin-1, and tumor necrosis factor alpha, which are cytokines involved in the inflammation process. Ocular infections by C trachomatis and sometimes C pneumoniae strains cause acute purulent conjunctivitis either due to infection of the neonate during passage through the birth canal or due to subsequent infections leading to scarring of the conjunctiva and to blindness subsequent to mucopurulent follicular conjunctivitis. C trachomatis infection also spreads through sexual contact when urethritis or cervicitis is present. The genital tract infection serves as a source of infectious elementary bodies for the eyes.

• #9 DigitalCommons@UNMC

  https://digitalcommons.unmc.edu/etd/789/

  Chlamydia trachomatis is both the leading cause of non-congenital preventable blindness in developing nations and the leading source of bacterial sexually transmitted infections. […] As an obligate intracellular pathogen, Chlamydia has an absolute requirement on gaining entry into its host, which is accomplished by manipulating the host actin cytoskeleton to assemble engulfment structures that drive pathogen entry. […] In support of this, Chlamydia secretes the effectors TarP and TmeA via a type-III secretion system, whose respective signaling outputs operate synergistically to generate rapid actin kinetics and efficient pathogen engulfment. […] Rapid actin recruitment characteristic of invading Chlamydia is derived from a collaborative interaction between the actin nucleators formin and Arp2/3, which is established on the basis of signaling from both TarP and TmeA.

• #10 DigitalCommons@UNMC

  https://digitalcommons.unmc.edu/etd/789/

  Moreover, TarP signaling promotes the recruitment of focal adhesion proteins FAK, vinculin, Talin, and MPRIP, resulting in the assembly of a myosin-sensitive scaffold centered around TarP that accelerates both actin recruitment and turnover. […] The actin network generated by TarP and TmeA signaling drives the recruitment and activation of host dynamin-2, which catalyzes membrane scission of Chlamydia-containing vacuoles in support of rapid pathogen entry. […] Additionally, dynamin activity is co-regulated alongside actin turnover, implying a functional link between dynamin-dependent scission and actin depolymerization. […] Loss of either TarP or TmeA results in inefficient pathogen uptake, which is characterized by macropinocytotic uptake in TarP-deficient strains, and by deficiencies in both actin remodeling and dynamin 2 activation in TmeA-deficient strains.

• #11 A renewed tool kit to explore Chlamydia… | F1000Research

  https://f1000research.com/articles/8-935

  The elementary body (EB) is the environmentally stable form of the pathogen that binds and invades target cells. The EB then transitions into the larger intracellular reticulate body (RB) form. RBs replicate and secrete proteins across the parasitophorous membrane-bound vacuole (inclusion) to modulate multiple host cellular functions that benefit the bacterium. […] All Chlamydiae encode a type III secretion (T3S) system to deliver a defined cohort of bacterial proteins (T3S effectors) directly into the host cell. The Chlamydia trachomatis EB T3S effectors modify the cytoskeleton and stimulate bacterial uptake into a membrane-bound vacuole that is rapidly segregated from degradative trafficking pathways. […] A subset of T3S effectors are inserted into the inclusion membrane. These inclusion membrane proteins (Incs), which are secreted throughout the infectious life cycle, are diverse (~5% of the total coding potential of C. trachomatis) and their molecular function is just beginning to be understood.

• #12 A renewed tool kit to explore Chlamydia… | F1000Research

  https://f1000research.com/articles/8-935

  As the inclusion matures, it is increasingly encased by a network of F-actin, microtubules, intermediate filaments, and septins, which help confine the bacteria within the inclusion and limit recognition of bacterial products by innate immune sensors. […] Much of our understanding of the cell biology of how Chlamydia interacts with target cells and the molecular mechanisms it uses to manipulate cellular processes is based on observations made in infected cancer cell lines, which in addition to being metabolically and genetically adapted for proliferation, lack positional cues that are available only in the context of tissues. […] The greatest single advance in Chlamydia biology over the past decade has been the development of methods to perform genetic analysis of C. trachomatis mutants and increasingly robust molecular genetic tools to transform Chlamydia with recombinant DNA.

• #13 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Chlamydia-Infection-Pathophysiology.aspx

  Chlamydia infection is caused by the bacterium Chlamydia trachomatis and is one of the most common sexually transmitted diseases in the world. […] The Chlamydia bacteria invades and infects the host cells, which they depend on to provide them with nutrients for survival. […] Once the Chlamydia bacteria are starved of nutrients such as vitamins or iron, they stop dividing and grow to an abnormally large size. […] However, some infections persist and may lead to serious problems such as pelvic inflammatory disease in women and epididymis in men. The bacteria can cause infertility in both men and women.

• #14 Persistence in Chlamydia | IntechOpen

  https://www.intechopen.com/chapters/85386

  Persistence is an important cause of recurrent Chlamydial disease characterized by chronic inflammation and tissue damage in epithelial cells. […] Chlamydia can also transform into a third morphologic subtype under certain conditions. When Chlamydiae experience physiologic stressors, RBs can transform into abnormally large bacteria known as an aberrant body (AB). […] ABs are characterized by their non-infectious hibernating state, allowing them to re-enter the normal biphasic life cycle once the underlying stressor subsides to continue producing infectious EBs. […] Chlamydia employs several mechanisms to interfere with the host innate immune response to persist within the host cell. […] The NFB pathway may be modulated by several different Chlamydial proteins and mechanisms, all of which can interfere with NFB-mediated gene transcription and regulation.

• #14 Persistence in Chlamydia | IntechOpen

  https://www.intechopen.com/chapters/85386

  Chlamydia spp. are important causes of acute and persistent/chronic infections. All Chlamydia spp. display a unique biphasic developmental cycle alternating between an infectious elementary body (EB) and a replicative form, the reticulate body (RB), followed by the multiplication of RBs by binary fission and progressive differentiation back into EBs. […] During its intracellular life, Chlamydia employs multiple mechanisms to ensure its persistence inside the host. These include evasion of diverse innate immune responses, modulation of host cell structure and endocytosis, inhibition of apoptosis, activation of pro-signaling pathways, and conversion to enlarged, non-replicative but viable aberrant bodies (ABs). […] In the context of Chlamydia, persistence or Chlamydial stress response is the reversible inhibition of cell division that interrupts the pathogens developmental cycle in the presence of unfavorable growth conditions.

• #15 Persistence in Chlamydia | IntechOpen

  https://www.intechopen.com/chapters/85386

  Various mechanisms of IFN–induced persistence have been proposed. IFN- activates the catabolic depletion of L-tryptophan (Trp) via indoleamine-2,3-dioxygenase (IDO), the enzyme that degrades tryptophan. […] During the persistent state, Chlamydiae can activate pro-survival pathways and inhibit apoptosis to ensure long-term survival inside the cells. […] Chlamydia must protect the host cell from succumbing to stress-induced death before the Chlamydial developmental cycle is complete. […] The ability of Chlamydiae to induce host-cell apoptosis under some circumstances and actively inhibit apoptosis to complete their obligate intracellular growth has been extensively studied for decades. […] Chlamydia can manipulate the mitochondrial morphology to promote their own replication or to escape from host immune responses.

• #16 Chlamydia Trachomatis | British Society for Immunology

  https://www.immunology.org/public-information/bitesized-immunology/pathogens-disease/chlamydia-trachomatis

  Normally the female reproductive tract does not have associated organised lymphoid tissue but there are dendritic cells, macrophages and a few resident lymphocytes scattered throughout the four main epithelial areas, the vagina, the cervix, the uterus and the Fallopian tubes. Ct infection usually occurs in the lower genital tract and attracts different types of immune cells such as lymphocytes, macrophages and dendritic cells to infiltrate the epithelium. At the site of infection there is a strong inflammatory reaction mediated mainly by CD4+ T cells with a Th1 phenotype to clear the infection. These cells produce interferon-γ (IFN-γ) which is known to inhibit chlamydial reproduction. However, there is evidence that the concentration of IFN-γ is critical to the outcome of infection; high levels of IFN-γ are associated with the clearance of the infection whilst low levels can allow the bacteria to persist without replicating. Ct infection can persist for several years and reinfection is common. It has been shown that reinfection can result in a strong secondary immune response and the increased inflammation may cause further damage to the reproductive tract. This has been suggested to be the case in chronic pelvic inflammatory disease. If the infection spreads higher up the tract to the uterus and Fallopian tubes, the risk of ectopic pregnancy and infertility due to tubal damage is high. It remains unclear how much damage is caused by Ct and how much by the host immune response.

• #17

  https://www.jci.org/articles/view/119136

  Secretion of proinflammatory cytokines by epithelial cells in response to Chlamydia infection suggests a central role for epithelial cells in chlamydial pathogenesis. […] Chlamydia species infect epithelial cells at mucosal surfaces, and are major causes of sexually transmitted diseases. Infection is characterized by inflammation which is exacerbated upon reinfection, ultimately leading to tissue damage and scarring. […] Although central for the development of disease manifestations, little is known about the mechanisms that initiate and sustain the inflammatory response to Chlamydia. […] Infection of cervical and colonic epithelial cells with Chlamydia trachomatis and Chlamydia psittaci is shown in the present studies to upregulate mRNA expression and secretion of the proinflammatory cytokines IL-8, GRO alpha, GM-CSF, and IL-6.

• #17

  https://www.jci.org/articles/view/119136

  Moreover, epithelial cell lines and primary endocervical epithelial cells released IL-1alpha after Chlamydia infection, and increased secretion of the proinflammatory cytokines could be inhibited by anti-IL-1alpha. […] This suggests that IL-1alpha, released following lysis of infected epithelial cells, may amplify the inflammatory response by stimulating additional cytokine production by noninfected neighboring cells. […] These findings suggest a novel pathophysiologic concept wherein the acute host response to Chlamydia at mucosal surfaces is primarily initiated and sustained by epithelial cells, the first and major targets of chlamydial infection.

• #18 About Chlamydia | Chlamydia | CDC

  https://www.cdc.gov/chlamydia/about/index.html

  Chlamydia is a common STI that can cause infection among men and women. It can cause permanent damage to a woman’s reproductive system. This can make it difficult or impossible to get pregnant later. Chlamydia can also cause a potentially fatal ectopic pregnancy (pregnancy that occurs outside the womb). […] The initial damage that chlamydia causes often goes unnoticed. However, chlamydia can lead to serious health problems. […] In women, untreated chlamydia can cause pelvic inflammatory disease (PID). Some of the complications of PID are: Formation of scar tissue that blocks fallopian tubes, Ectopic pregnancy (pregnancy outside the womb), Infertility (not being able to get pregnant), Long-term pelvic/abdominal pain. […] Men rarely have health problems from chlamydia. The infection can cause a fever and pain in the tubes attached to the testicles. This can, in rare cases, lead to infertility. […] Untreated chlamydia may also increase your chances of getting or giving HIV.

• #19 Patient education: Chlamydia (Beyond the Basics) – UpToDate

  https://www.uptodate.com/contents/chlamydia-beyond-the-basics

  Chlamydia infections are caused by a bacterium, Chlamydia trachomatis, which can infect the genital and rectal tract of women and men. The infection is spread during intimate sexual contact. A man does not have to ejaculate to spread the infection. Women can have rectal infection even if they do not practice anal sex, because chlamydia can also spread to the rectum from infected vaginal secretions. […] Chlamydia in women can lead to a serious infection called pelvic inflammatory disease (PID). If chlamydia is not treated, up to 30 percent of women may develop PID. PID can cause scarring of the fallopian tubes, which can lead to infertility and an increased risk of ectopic pregnancy or chronic pelvic pain. […] If you have (or think you may have) chlamydia and are pregnant or want to get pregnant, it’s important to get tested and treated as soon as possible. Untreated infection can cause serious problems in pregnancy, including miscarriage and premature birth. It’s also possible to pass the infection on to your baby during delivery. This can cause conjunctivitis that can damage the baby’s eyes and affect vision over time. Newborns infected with chlamydia can also develop pneumonia.

• #19 Patient education: Chlamydia (Beyond the Basics) – UpToDate

  https://www.uptodate.com/contents/chlamydia-beyond-the-basics

  For most infections in nonpregnant individuals, experts recommend taking doxycycline twice daily for seven days by mouth, especially if there is a concern for rectal infection. […] Treatment is important for you and anyone you have had sex with recently, even if they have no symptoms or recently tested negative for chlamydia. This is because not all infections cause symptoms, and because the test might not detect a recent infection, which could have been the source of your infection. […] The most effective way to prevent chlamydia is to avoid sexual contact. Because this is not a realistic option for most people, the following tips are recommended to reduce the risk of getting or spreading chlamydia: Use condoms every time you have sex.

• #20 Current Understanding and Gaps in Knowledge of Chlamydia trachomatis Infection

  https://www.scientificarchives.com/article/current-understanding-and-gaps-in-knowledge-of-chlamydia-trachomatis-infection

  From the above, it follows that serious sequelae due to chlamydial infection are observed only if it is chronic and persistent inflammation (sustained and harmful possibly due to residual antigens and not the persistence of viable bacteria) is the cause of fibrosis and the scars that characterize all chlamydial diseases. […] The molecular mechanism of bacterial persistence is pointed out: the deprivation of tryptophan and cysteine, essential amino acids for the expression of late expression proteins such as MOMP and proteins rich in cysteines that cause the cessation of the division of the reticular bodies as well as dedifferentiation of them in elementary bodies, in other words the persistence of C. trachomatis is a consequence of undifferentiated intracellular particles; and the abrogation of cell division although DNA replication and segregation persist. […] There are several strategies that C. trachomatis uses to ensure its persistence in the host and produce chronic infection and clinical complications.

• #20 Current Understanding and Gaps in Knowledge of Chlamydia trachomatis Infection

  https://www.scientificarchives.com/article/current-understanding-and-gaps-in-knowledge-of-chlamydia-trachomatis-infection

  Chlamydia trachomatis is a bacterial infection that most frequently causes sexually transmitted infection in the world, therefore, it is considered a serious public health problem. […] The information obtained was grouped into 7 categories as a result of the analysis of relevant ideas. There are many aspects to be revealed in terms of pathogenesis, biology of the microbial agent, and treatment, hence the need to generate new knowledge in this regard and to carry out thematic consolidations such as the one presented here. […] In women C. trachomatis is the cause of pelvic inflammatory disease, in men it is capable of infecting the accessory sexual glands and producing epididymitis, prostatitis, and urethritis (in the acute phase), and in both cases infertility. Furthermore, in men and women, already in the chronic or complicated phase, they generate glaucoma, endocarditis, coronary heart disease, chronic asthma, reactive arthritis, hepatitis and urethral syndrome, among others, which is why the pathogenic mechanisms involved in them are studied intensely and continuously the genesis of the aforementioned complications.

• #20 Current Understanding and Gaps in Knowledge of Chlamydia trachomatis Infection

  https://www.scientificarchives.com/article/current-understanding-and-gaps-in-knowledge-of-chlamydia-trachomatis-infection

  Several strategies have been proposed through which C. trachomatis leads to chronic infection, among them: asymptomatic infections by remaining silent that favor bacterial progression towards the most internal tissues (refers to the fact that the pathogenic agent possibly spreads found in an atypical, intracellular and metabolically less active state that is difficult to resolve not only by the host defense system, but also by antibiotic therapy); and variable immunodominant antigenic epitopes of the major outer membrane protein (MOMP) consequently, specific immunity against strains is not produced (therefore multiple reinfection by different serotypes and by the same serotype is possible), but an autopathological immune response may occur. […] The accumulation of heat shock proteins (hsp60) as a consequence of multiple reinfections by C. trachomatis, a protein with a high proportion of identity with the human protein, therefore autoimmunity can occur when human tolerance to its own hsp60 is broken; and that the antibodies generated by C. trachomatis infection do not inactivate the parasites inside the cells.

• #21 Chlamydiae as Pathogens: New Species and New Issues – Volume 2, Number 4—October 1996 – Emerging Infectious Diseases journal – CDC

  https://wwwnc.cdc.gov/eid/article/2/4/96-0406_article

  Interesting findings in three areas of C. trachomatis pathogenesis further delineate the complex bacteria-host relationship in disease and may have implications for vaccine design. These new observations include the extensive but unexpected polymorphism of the major outer membrane protein (MOMP), the evidence for genetic susceptibility to disease, and the association of antibody response to the 60 kDa heat shock protein (CHSP60) with the development of adverse sequelae following ocular and genital infections. […] The basis for MOMP antigenic variation is allelic polymorphism at the omp-1 locus, and immune selection appears to be occurring in host populations frequently exposed to C. trachomatis. […] The frequency of HLA class II alleles was similar among cases and controls suggesting that, if class II restricted T-cell responses are important in immunopathology, they were not targeted at single epitopes.

• #22 Chlamydiae as Pathogens: New Species and New Issues – Volume 2, Number 4—October 1996 – Emerging Infectious Diseases journal – CDC

  https://wwwnc.cdc.gov/eid/article/2/4/96-0406_article

  The association between antibody response to CHSP60 and PID, ectopic pregnancy, tubal infertility, and trachoma has been documented. […] At present, it remains unclear whether antibody to CHSP60 is causally involved in chlamydial immunopathogenesis or is merely a marker of persistent chlamydial infection.

• #23 Actin Recruitment to the Chlamydia Inclusion Is Spatiotemporally Regulated by a Mechanism That Requires Host and Bacterial Factors | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0046949

  Perhaps the salient finding of this work was the central role of Chlamydia type III secreted proteins in actively controlling actin coat assembly, and that extrusion was also dependent on chlamydial type III secreted product(s). […] Our data demonstrates that actin coating of inclusions is a key determining factor for extrusion; disruption of coat formation led to a marked reduction in the number of extrusions produced.

• #24

  https://scholars.duke.edu/individual/pub1557146

  Chlamydia trachomatis uses the effector protein TepP to transiently disassemble tight junctions early during infection. […] TepP alters the tyrosine phosphorylation status of host proteins involved in cytoskeletal regulation, including the filamentous actin-binding protein EPS8. […] We determined that TepP and EPS8 are necessary and sufficient to remodel tight junctions and that the ensuing disruption of epithelial barrier function promotes secondary invasion events. […] The genetic deletion of EPS8 renders epithelial cells and endometrial organoids resistant to TepP-mediated tight junction remodeling. […] Finally, TepP and EPS8 promote infection in murine models of infections, with TepP mutants displaying defects in ascension to the upper genital tract. […] These findings reveal a non-canonical function of EPS8 in the disassembly of epithelial junctions and an important role for Chlamydia pathogenesis.

• #25 Attachment and Entry of Chlamydia Have Distinct Requirements for Host Protein Disulfide Isomerase | PLOS Pathogens

  https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1000357

  Chlamydia is an obligate intracellular pathogen that causes a wide range of diseases in humans. Attachment and entry are key processes in infectivity and subsequent pathogenesis of Chlamydia, yet the mechanisms governing these interactions are unknown. […] To advance our understanding of the role of PDI in Chlamydia infection, we used RNA interference to establish that cellular PDI is essential for bacterial attachment to cells, making PDI the only host protein identified as necessary for attachment of multiple species of Chlamydia. […] Our findings demonstrate that PDI has two essential and independent roles in the process of chlamydial infectivity: it is structurally required for chlamydial attachment, and the thiol-mediated oxido-reductive function of PDI is necessary for entry. […] While PDI is necessary for Chlamydia attachment to cells, the bacteria do not appear to utilize plasma membrane-associated PDI as a receptor, suggesting that Chlamydia binds a cell surface protein that requires structural association with PDI.

• #26 Attachment and Entry of Chlamydia Have Distinct Requirements for Host Protein Disulfide Isomerase | PLOS Pathogens

  https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1000357

  We have determined that although cellular PDI is required for both Chlamydia attachment and entry the requirement is mechanistically different in the two processes. PDI cell surface enzymatic activity was necessary for entry of bacteria into cells. In contrast, Chlamydia attachment to host cells required PDI but was independent of cell surface PDI enzymatic activity. […] These data show that while PDI is necessary for chlamydial attachment, the function of PDI in attachment is independent of the protein’s enzymatic activity. […] From these results it can be concluded that PDI serves two distinct yet essential functions for Chlamydia attachment and entry. The role of PDI in attachment is not enzymatic but perhaps limited to a structural or chaperone function, whereas subsequent bacterial entry requires PDI enzymatic activity. […] We established using PDI-specific chemical inhibitors, anti-PDI antibodies, and chemical reduction of bound organisms that the function of PDI in chlamydial infectivity requires surface accessible PDI.

• #27 Effect of Time of Day of Infection on Chlamydia Infectivity and Pathogenesis | Scientific Reports

  https://www.nature.com/articles/s41598-019-47878-y

  Genital chlamydia infection in women causes complications such as pelvic inflammatory disease and tubal factor infertility, but it is unclear why some women are more susceptible than others. […] Possible factors, such as time of day of chlamydia infection on chlamydial pathogenesis has not been determined. […] The results suggest that the time of day of infection influences chlamydial pathogenesis, it indicates a possible association between complications from chlamydia infection and host circadian clock, which may lead to a better understanding of chlamydial pathogenesis. […] Understanding the role of circadian rhythms on bacterial infections has been of interest for a long time. […] It is unclear if circadian clocks influence the pathogenesis of genital chlamydia infection. […] The results reveal that mice can resist genital C. muridarum infection when they are infected in the early active period than during the early rest period, indicating a direct linkage between the lesions observed after infection with the time of day of infection.

• #28 Effect of Time of Day of Infection on Chlamydia Infectivity and Pathogenesis | Scientific Reports

  https://www.nature.com/articles/s41598-019-47878-y

  The results reveal that the time of day in which mice are exposed to pathogen plays an important role in C. muridarum infectivity. […] The results indicate that the increase in infectivity observed in the mice infected during the early rest period has a positive correlation to the lesions observed in them. […] The observation corroborates the hypothesis that the hosts physiologic state at the time of infection, which might be controlled by circadian clocks, could influence the intensity and pathologic outcomes of genital chlamydia infection. […] The results suggest that the effect of time of day on chlamydial pathogenesis is the same during a repeat infection, furthermore time of day of infection influences the overall fertility rate of the infected mice. […] The results suggest that the effect of time of day of infection was not strain specific or age dependent. […] Time of day of chlamydia infection appears to have an influence on its pathogenesis and disease progression. […] This can be linked to the rhythmic changes in the production of chemokines/cytokines and antibodies.

• #29 Researchers Discover Molecule That Can Kill Chlamydia Without Harming Healthy Bacteria – INDIA New England News

  https://indianewengland.com/researchers-discover-molecule-that-can-kill-chlamydia-without-harming-healthy-bacteria/

  In a significant breakthrough, an international team of scientists has identified a molecule capable of selectively killing Chlamydia trachomatis, the bacterium responsible for the world’s most common bacterial sexually transmitted infection, while leaving beneficial bacteria unharmed. […] The bacterium operates much like a virus, invading human cells and transforming them into safe havens where it can replicate. This stealthy behavior makes it especially difficult to treat without disrupting the body’s healthy bacterial ecosystem. […] Using large-scale chemical screening methods, the researchers examined thousands of molecules to pinpoint those capable of stopping Chlamydia trachomatis in laboratory-grown human cells. The most promising candidate was found to inhibit the bacterium’s ability to produce fatty acids, a key process for its survival and replication.

• #29 Researchers Discover Molecule That Can Kill Chlamydia Without Harming Healthy Bacteria – INDIA New England News

  https://indianewengland.com/researchers-discover-molecule-that-can-kill-chlamydia-without-harming-healthy-bacteria/

  While chlamydia often causes mild or no symptoms, untreated infections can lead to severe complications, particularly in women. Long-term consequences include chronic pelvic pain, infertility, and increased risk of ectopic pregnancy. Research also suggests a possible link between chronic chlamydia infections and cancers of the cervix and ovaries. […] The findings bring renewed hope for more precise, less disruptive treatment options at a time when antibiotic resistance continues to threaten public health globally.

• #30 Azithromycin – Uses, Side Effects, Composition, Dosage & Price PACE Hospitals – Best Hospitals in Hitech City, Hyderabad, India | Near Madhapur, Kukatpally, KPHB, Kondapur, Gachibowli, Jubilee Hills, Banjara HillsPACE Hospitals Contact Nu

  https://www.pacehospital.com/azithromycin-uses-side-effects-composition-dosage-price

  Azithromycin plays a key role against various microorganisms such as Mycoplasma, Chlamydia, Neisseria, Staphylococcus and Streptococcus species. […] Azithromycin works by prohibiting the attachment of 50s ribosomal unit in the bacteria thus preventing translation of mRNA, thereby disrupting the protein synthesis and bacterial growth.

• #31 National STD Curriculum Podcast – episode – expert-interviews – new-chlamydia-pathophysiology-research – National STD Curriculum

  https://www.std.uw.edu/podcast/episode/expert-interviews/new-chlamydia-pathophysiology-research

  And we used three drugs. We used ofloxacin, which is a quinolone, we used tetracycline (TET), and we used chloramphenicol. These are different drugs, they target different pathways within cells, and we were just trying this out. […] And so this began this line of investigation, what is going on in these cells treated with ofloxacin? […] And what was remarkable about that, and what Scott’s work really added here, is that the forms that recovered were absolutely invisible at the beginning, in his experiments and in our experiments. And they appeared to be truly dormant forms that were frozen at some very early point in development before these microbes could express any of the proteins that we were looking at. […] So, these are antibiotics that we don’t associate with the formation of aberrant forms.

• #32 National STD Curriculum Podcast – episode – expert-interviews – new-chlamydia-pathophysiology-research – National STD Curriculum

  https://www.std.uw.edu/podcast/episode/expert-interviews/new-chlamydia-pathophysiology-research

  So, this is a dormancy or persistence that appears to be separate from what people say with aberrancy, and that’s what’s probably the novel aspect of the work that we are describing. […] So, the Chlamydia is existing in a completely different form that was not recognized until now. […] I think, yes. The question is whether or not these forms are elementary bodies or if they are in some state that’s between an elementary body and a reticulate body. […] Persistence is a key part of the natural history of almost all Chlamydia during infection and disease, I would say certainly in humans. […] Persistence discusses the organisms that are genetically identical, but a fraction of which resist either the drug, or the immune attack, or any other stress in the cell, and once the stress is removed, that organism grows out.

• #33 National STD Curriculum Podcast – episode – expert-interviews – new-chlamydia-pathophysiology-research – National STD Curriculum

  https://www.std.uw.edu/podcast/episode/expert-interviews/new-chlamydia-pathophysiology-research

  In the end, what this is telling us is that our models of aberrancy are maybe not complete, and that’s sort of impacting our ability to understand persistence in a clinical sense. […] So, in addition to aberrancy, are there other aspects of chlamydial biology that lead to clinical persistence? […] Yes. And, as always, once you discover something that’s kind of interesting, you try to dive back into the literature and understand what is known and not known. […] And the logic that developed out of those studies, which continue to this day, is that there’s probably two different metabolic processes that are affected by quinolone antibiotics. […] So, basically, we’re just forcing more organisms to go into this static role rather than lytic role. […] So, how does Chlamydia know when to start replicating? It’s one of our big questions.

• #34 National STD Curriculum Podcast – episode – expert-interviews – new-chlamydia-pathophysiology-research – National STD Curriculum

  https://www.std.uw.edu/podcast/episode/expert-interviews/new-chlamydia-pathophysiology-research

  My primary interests here involve trying to identify the state of this dormant form. Is it truly a unique form within an infected cell, does it exist persistently in that cell, and can we relate that to what might be happening in patients? […] But, certainly vaccination is a very challenging subject in this organism. […] So, then the shift becomes, well, we need to target as an intracellular pathogen with CD8, T cells, things like that, and I think that becomes more challenging from a vaccine standpoint.

• #35 Pathogenesis of Chlamydia induced pelvic inflammatory disease. | Sexually Transmitted Infections

  https://sti.bmj.com/content/75/1/21

  Further research is necessary to elucidate the pathogenesis of chlamydial PID. […] It is hoped that these endeavours will eventually lead to a vaccine to prevent not only chlamydia infection, but also chlamydia associated infertility, ectopic pregnancy, and chronic pelvic pain. […] In the meantime we need to develop strategies to prevent primary and secondary chlamydia infection and its sequelae. […] Recently, Scholes et. al demonstrated that a population based approach to identify and test women at high risk for cervical C trachomatis infection effectively reduced risk of PID. […] Hopefully, through the use of public health measures, we can see similar decreases of chlamydia associated genital tract disease worldwide.

• #36 Chlamydia trachomatis – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/chlamydia/symptoms-causes/syc-20355349

  Chlamydia is caused by Chlamydia trachomatis (truh-KOH-muh-tis) bacteria and spread through oral, vaginal or anal sex. […] The Chlamydia trachomatis bacterium is most commonly spread through vaginal, oral and anal sex. It also is possible for the bacterium to spread in pregnancy, during delivery of the baby. Chlamydia can cause pneumonia or a serious eye infection in the newborn. […] Chlamydia trachomatis can be associated with: […] Chlamydia infections can cause scarring and obstruction in the fallopian tubes, which might lead to infertility. […] A medicine called doxycycline may be an option to prevent infection among people at higher risk than average of getting chlamydia. Higher risk groups include men who have sex with men and transgender women. Taking doxycycline within 3 days of sexual activity lowers the risk of an infection with the bacteria that cause chlamydia.

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