Materiały źródłowe

• #1 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20230616/New-method-offers-insights-into-mechanisms-of-staphylococcal-pathogenesis.aspx

  Nearly one in three people globally unknowingly carries Golden staph, or Staphylococcus aureus, in their nose or on their skin. […] While the bacterium is harmless to most, it can lead to serious infection and even death if it enters the bloodstream through a cut, surgical wound or catheter. […] Dr Hachani explained the innovative approach, developed by his research team, is key to understanding how Golden staph behaves inside cells and gaining valuable knowledge about the bacteria’s ability to survive and thrive in humans. […] We identified the genes that control the bacteria’s ability to persist inside host cells without killing them. This is an important advance to understand how S. aureus can cause lethal infections. […] Using this platform, we were able to identify mutations in the bacteria that are clinically relevant and promote their ability to persist inside the body. This new knowledge will guide research to find new ways to combat these infections.

• #2 Staphylococcus aureus bacteria turns immune system against itself | University of Chicago News

  https://news.uchicago.edu/story/staphylococcus-aureus-bacteria-turns-immune-system-against-itself

  Around 20 percent of all humans are persistently colonized with Staphylococcus aureus bacteria, a leading cause of skin infections and one of the major sources of hospital-acquired infections, including the antibiotic-resistant strain MRSA. […] University of Chicago scientists have recently discovered one of the keys to the immense success of S. aureus the ability to hijack a primary human immune defense mechanism and use it to destroy white blood cells. […] These bacteria have endowed themselves with weapons to not only anticipate every immune defense, but turn these immune defenses against the host as well, said Olaf Schneewind, professor and chair of microbiology and senior author of the paper. […] However, S. aureus infection sites are often marked by an absence of macrophages, indicating the bacteria somehow defend themselves against the immune system.

• #3 Staphylococcus – Medical Microbiology – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK8448/

  Staphylococci can cause many forms of infection. (1) S aureus causes superficial skin lesions (boils, styes) and localized abscesses in other sites. (2) S aureus causes deep-seated infections, such as osteomyelitis and endocarditis and more serious skin infections (furunculosis). (3) S aureus is a major cause of hospital acquired (nosocomial) infection of surgical wounds and, with S epidermidis, causes infections associated with indwelling medical devices. (4) S aureus causes food poisoning by releasing enterotoxins into food. (5) S aureus causes toxic shock syndrome by release of superantigens into the blood stream. (6) S saprophiticus causes urinary tract infections, especially in girls. (7) Other species of staphylococci (S lugdunensis, S haemolyticus, S warneri, S schleiferi, S intermedius) are infrequent pathogens.

• #4 Staphylococcal Infections – Infectious Diseases – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/infectious-diseases/gram-positive-cocci/staphylococcal-infections

  Staphylococci cause disease by […] Direct tissue invasion is the most common mechanism for staphylococcal disease, including the following: […] Multiple exotoxins are sometimes produced by staphylococci. Some have local effects; others trigger cytokine release from certain T cells, causing serious systemic effects (eg, skin lesions, shock, organ failure, death). […] Toxin-mediated staphylococcal diseases include the following: […] Staphylococcal toxic shock syndrome may result from use of vaginal tampons or other devices or complicate any type of S. aureus infection (eg, postoperative wound infection, infection of a burn, skin infection). […] Staphylococcal scalded skin syndrome, which is caused by several toxins termed exfoliatins, is an exfoliative dermatitis of childhood characterized by large bullae and peeling of the upper layer of skin.

• #5 Staphylococcus – Medical Microbiology – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK8448/

  S aureus expresses many potential virulence factors. (1) Surface proteins that promote colonization of host tissues. (2) Factors that probably inhibit phagocytosis (capsule, immunoglobulin binding protein A). (3) Toxins that damage host tissues and cause disease symptoms. Coagulase-negative staphylococci are normally less virulent and express fewer virulence factors. S epidermidis readily colonizes implanted devices. […] S aureus expresses many cell surface-associated and extracellular proteins that are potential virulence factors. For the majority of diseases caused by this organism, pathogenesis is multifactorial. Thus it is difficult to determine precisely the role of any given factor. This also reflects the inadequacies of many animal models for staphylococcal diseases. […] However, there are correlations between strains isolated from particular diseases and expression of particular factors, which suggests their importance in pathogenesis. With some toxins, symptoms of a human disease can be reproduced in animals with pure proteins. The application of molecular biology has led to recent advances in the understanding of pathogenesis of staphylococcal diseases. Genes encoding potential virulence factors have been cloned and sequenced and proteins purified. This has facilitated studies at the molecular level on their modes of action, both in in vitro and in model systems. In addition, genes encoding putative virulence factors have been inactivated, and the virulence of the mutants compared to the wild-type strain in animal models. Any diminution in virulence implicates the missing factor. If virulence is restored when the gene is returned to the mutant then Molecular Koch’s Postulates have been fulfilled. Several virulence factors of S aureus have been confirmed by this approach.

• #6 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Staphylococcus-Aureus-Virulence-Factors.aspx

  The virulence of S. aureus lies in its ability to adapt to environmental pressures and immune defenses quickly. A central feature of its survival strategy is the accessory gene regulatory (Agr) two-component system (TCS), which helps control the production of key virulence factors. […] When bacterial populations increase within host tissues, the Agr system is activated, triggering toxin production. As the infection progresses, Agr activity is downregulated, helping the bacteria evade immune detection. […] One of its key toxins, -toxin, compromises epithelial barriers by activating the metalloproteinase ADAM10, which disrupts cell junctions. […] To adhere to host tissues, S. aureus uses surface proteins from the MSCRAMM family such as staphylococcal protein A (SpA), fibronectin-binding proteins (FnbpA/B), and clumping factors (ClfA/B) which bind to components like collagen and fibrinogen.

• #7 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Staphylococcus-Aureus-Virulence-Factors.aspx

  The virulence of S. aureus lies in its ability to adapt to environmental pressures and immune defenses quickly. A central feature of its survival strategy is the accessory gene regulatory (Agr) two-component system (TCS), which helps control the production of key virulence factors. […] When bacterial populations increase within host tissues, the Agr system is activated, triggering toxin production. As the infection progresses, Agr activity is downregulated, helping the bacteria evade immune detection. […] One of its key toxins, -toxin, compromises epithelial barriers by activating the metalloproteinase ADAM10, which disrupts cell junctions. […] To adhere to host tissues, S. aureus uses surface proteins from the MSCRAMM family such as staphylococcal protein A (SpA), fibronectin-binding proteins (FnbpA/B), and clumping factors (ClfA/B) which bind to components like collagen and fibrinogen.

• #8 VFDB – pathogenesis of Staphylococcus

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

  About Staphylococcus General information: Gram-positive spherical bacteria belong to Micrococcaceae family. Classified into two major groups: aureus and non-aureus. S. aureus is one of the major causes of community-acquired and hospital-acquired infection. Of the non-aureus species, S. epidermis is the most clinically significant. Characteristics: Primarily an extracellular pathogen. Adherence is mediated by surface protein adhesins called MSCRAMMs (microbial surface components recognizing adhesive matrix molecules). One feature contributes to the virulence of S. epidermidis is the ability to adhere to plasitic and form a biofilm. Disease: S. aureus: a wide variety of diseases, ranging form superficial abscesses and wound infections to deep and systemic infections such as osteomyelitis, endocarditis and septicaemia. Toxic-shock syndrome, staphylococcal scarlet fever, scalded skin syndrome. S. epidermidis: catheter-associated infections, biofilms on plastic implants, endocarditis. Major virulence factors in Staphylococcus: Adherence Clumping factor CNA (Collagen binding protein) Eap/Map (Extracellular adherence protein/MHC analogous protein) EbpS (Elastin-binding protein) FnBPs (Fibronectin binding proteins) SDr (Ser-Asp rich proteins) Effector delivery system Type VII secretion system Exotoxin -hemolysin -hemolysin -hemolysin -hemolysin PVL (Panton-Valentine leukocidin) SE (Staphylococcal enterotoxin) SpA (Staphylococcal protein A) SSLs (Staphylococcal superantigen-like proteins) TSST-1 (Toxic shock syndrome toxin-1) Exoenzyme Aureolysin Exfoliative toxin Hyaluronate lyase Lipase Staphopain Staphylocoagulase Staphylokinase V8 protease vWbp (Von Willebrand factor-binding protein) Immune modulation AdsA (Adenosine synthase A) Capsule CHIPS (Chemotaxis inhibitory protein of Staphylococcus) Sbi (Staphylococcal binder of immunoglobulin) SCIN (Staphylococcal complement inhibitor) Biofilm Intercellular adhesion proteins Nutritional/Metabolic factor Isd Genomic location of virulence-related genes in Staphylococcus:

• #9 Immune System Evasion Mechanisms in Staphylococcus aureus: Current Understanding – Journal of Pure and Applied Microbiology

  https://microbiologyjournal.org/immune-system-evasion-mechanisms-in-staphylococcus-aureus-current-understanding/

  One of the most important virulence factors is surface proteins which promote and encourage the binding and the attachment processes of this bacterium to the host cells surfaces. To avoid recognition from the host immune cells, the surface proteins combined with the blood proteins that lead to aid the bacterium to survive and cause damage to host tissues. […] Moreover, S. aureus can generate another harmful type of toxins such as Panton-Valentine leukocidin (PVL) which cause pneumonia in children and Toxic Shock Syndrome Toxin-1 (TSST-1) which is associated with some cases of septicaemia due to the use of particular types of tampons. […] When S. aureus invade the host tissues, the innate immune system responds rapidly as an early defense against the bacterial invasion. This system consists of three important parts; (i) the complement system, (ii) phagocytes and (iii) antimicrobial peptides.

• #10 VFDB – pathogenesis of Staphylococcus

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

  About Staphylococcus General information: Gram-positive spherical bacteria belong to Micrococcaceae family. Classified into two major groups: aureus and non-aureus. S. aureus is one of the major causes of community-acquired and hospital-acquired infection. Of the non-aureus species, S. epidermis is the most clinically significant. Characteristics: Primarily an extracellular pathogen. Adherence is mediated by surface protein adhesins called MSCRAMMs (microbial surface components recognizing adhesive matrix molecules). One feature contributes to the virulence of S. epidermidis is the ability to adhere to plasitic and form a biofilm. Disease: S. aureus: a wide variety of diseases, ranging form superficial abscesses and wound infections to deep and systemic infections such as osteomyelitis, endocarditis and septicaemia. Toxic-shock syndrome, staphylococcal scarlet fever, scalded skin syndrome. S. epidermidis: catheter-associated infections, biofilms on plastic implants, endocarditis. Major virulence factors in Staphylococcus: Adherence Clumping factor CNA (Collagen binding protein) Eap/Map (Extracellular adherence protein/MHC analogous protein) EbpS (Elastin-binding protein) FnBPs (Fibronectin binding proteins) SDr (Ser-Asp rich proteins) Effector delivery system Type VII secretion system Exotoxin -hemolysin -hemolysin -hemolysin -hemolysin PVL (Panton-Valentine leukocidin) SE (Staphylococcal enterotoxin) SpA (Staphylococcal protein A) SSLs (Staphylococcal superantigen-like proteins) TSST-1 (Toxic shock syndrome toxin-1) Exoenzyme Aureolysin Exfoliative toxin Hyaluronate lyase Lipase Staphopain Staphylocoagulase Staphylokinase V8 protease vWbp (Von Willebrand factor-binding protein) Immune modulation AdsA (Adenosine synthase A) Capsule CHIPS (Chemotaxis inhibitory protein of Staphylococcus) Sbi (Staphylococcal binder of immunoglobulin) SCIN (Staphylococcal complement inhibitor) Biofilm Intercellular adhesion proteins Nutritional/Metabolic factor Isd Genomic location of virulence-related genes in Staphylococcus:

• #11 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Staphylococcus-Aureus-Virulence-Factors.aspx

  These interactions not only facilitate colonization but also promote immune evasion by inducing clot formation or platelet aggregation. […] Once established, S. aureus produces an extensive range of toxins and enzymes that enable it to invade tissues, evade immune responses, and extract nutrients. […] The bacterium also secretes exoproteins, including nucleases, proteases, lipases, hyaluronidase, and collagenase, which break down host tissues into usable nutrients. […] Additional virulence factors include exfoliative toxins A and B (ETA and ETB), which disrupt skin integrity, and EDIN exotoxins, which facilitate tissue invasion. […] Enterotoxins such as SEA, SEB, and SECn, along with toxic shock syndrome toxin-1 (TSST-1), act as superantigens, triggering uncontrolled immune activation, high fevers, and potentially fatal systemic inflammation.

• #12 Staphylococcus – Medical Microbiology – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK8448/

  The best characterized and most potent membrane-damaging toxin of S aureus is -toxin. It is expressed as a monomer that binds to the membrane of susceptible cells. […] The notion that -toxin is a major virulence factor of S aureus is supported by studies with the purified toxin in animals and in organ culture. Also, mutants lacking -toxin are less virulent in a variety of animal infection models. […] S aureus can express two different types of toxin with superantigen activity, enterotoxins, of which there are six serotypes (A, B, C, D, E and G) and toxic shock syndrome toxin (TSST-1). Enterotoxins cause diarrhea and vomiting when ingested and are responsible for staphylococcal food poisoning. When expressed systemically, enterotoxins can cause toxic shock syndrome (TSS) – indeed enterotoxins B and C cause 50% of non-menstrual TSS. TSST-1 is very weakly related to enterotoxins and does not have emetic activity. TSST-1 is responsible for 75% of TSS, including all menstrual cases.

• #13 The role of Staphylococcus aureus quorum sensing in cutaneous and systemic infections | Inflammation and Regeneration | Full Text

  https://inflammregen.biomedcentral.com/articles/10.1186/s41232-024-00323-8

  S. aureus possesses an auto-regulatory operon, Agr system, as a QS function. […] When AIP reaches the threshold, the transmembrane receptor on the cell surface, AgrC, is activated via autophosphorylation of its histidine protein kinase (HPK) domain. […] The P3 promoter regulates various toxins via RNAIII, a large regulatory RNA which has a complex secondary structure with several C-rich hairpin loops to interact with its target mRNAs. […] The essential virulence of PSM peptides rely on its cytolytic property, although not all PSMs from S. aureus are cytolytic. […] -Toxin or -hemolysin (hla) is a pore-forming toxin secreted as a soluble monomer. […] -Toxin contributes to the host lethal outcome in bloodstream infections through disseminated thrombosis caused by platelets and neutrophil intoxication.

• #14 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Staphylococcus-Aureus-Virulence-Factors.aspx

  S. aureus excels at evading the immune system. It often escapes from the bloodstream into tissues, where it forms abscesses dense bacterial clusters surrounded by immune cells that it effectively traps outside. […] The bacterium interferes with neutrophil function at multiple levels: it prevents their migration, suppresses their activation, and neutralizes their killing mechanisms. […] Enzymes such as superoxide dismutase (SOD), staphyloxanthin, and SPIN protect the bacterium from reactive oxygen species, while nucleases break down neutrophil extracellular traps (NETs). […] Immune shielding is further enhanced by biofilm formation, protective capsules, and cloaking within fibrin clots. […] Leukocidins, including Panton-Valentine leukocidin (PVL), are especially dangerous, as they destroy white blood cells even at low concentrations. […] Beyond antibody evasion, S. aureus also induces anti-inflammatory responses and adaptive immune tolerance, further complicating the hosts ability to eliminate the infection.

• #15 Staphylococcus – Medical Microbiology – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK8448/

  The best characterized and most potent membrane-damaging toxin of S aureus is -toxin. It is expressed as a monomer that binds to the membrane of susceptible cells. […] The notion that -toxin is a major virulence factor of S aureus is supported by studies with the purified toxin in animals and in organ culture. Also, mutants lacking -toxin are less virulent in a variety of animal infection models. […] S aureus can express two different types of toxin with superantigen activity, enterotoxins, of which there are six serotypes (A, B, C, D, E and G) and toxic shock syndrome toxin (TSST-1). Enterotoxins cause diarrhea and vomiting when ingested and are responsible for staphylococcal food poisoning. When expressed systemically, enterotoxins can cause toxic shock syndrome (TSS) – indeed enterotoxins B and C cause 50% of non-menstrual TSS. TSST-1 is very weakly related to enterotoxins and does not have emetic activity. TSST-1 is responsible for 75% of TSS, including all menstrual cases.

• #16 Staphylococcus – Medical Microbiology – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK8448/

  The best characterized and most potent membrane-damaging toxin of S aureus is -toxin. It is expressed as a monomer that binds to the membrane of susceptible cells. […] The notion that -toxin is a major virulence factor of S aureus is supported by studies with the purified toxin in animals and in organ culture. Also, mutants lacking -toxin are less virulent in a variety of animal infection models. […] S aureus can express two different types of toxin with superantigen activity, enterotoxins, of which there are six serotypes (A, B, C, D, E and G) and toxic shock syndrome toxin (TSST-1). Enterotoxins cause diarrhea and vomiting when ingested and are responsible for staphylococcal food poisoning. When expressed systemically, enterotoxins can cause toxic shock syndrome (TSS) – indeed enterotoxins B and C cause 50% of non-menstrual TSS. TSST-1 is very weakly related to enterotoxins and does not have emetic activity. TSST-1 is responsible for 75% of TSS, including all menstrual cases.

• #17 Skin Infections Caused by Staphylococcus aureus | HTML | Acta Dermato-Venereologica

  https://www.medicaljournals.se/acta/content/html/10.2340/00015555-3466

  Staphylococcus aureus is the most common pathogen involved in skin infections worldwide, regardless of the patients age, the climate or geographical area. The main skin clinical manifestations can be linked to a few toxins produced by the bacteria, which give rise to a rich and varied clinical spectrum. Panton Valentine leucocidin, exfoliatins, enterotoxins and toxin shock syndrome toxin 1 are the main toxins involved in most dermatological manifestations associated with S. aureus. […] The pathophysiology of staphylococcal impetigo is related to the local production of exfoliatin toxins A and B. The target protein of exfoliatins A and B is desmoglein 1, a desmosomal protein whose role is the cohesion between keratinocytes, and it is mainly located in the most superficial layer of the epidermis. The main consequence of the action of the toxin on desmoglein 1 is rupture of keratinocyte cohesion and formation of a bullae.

• #18 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Staphylococcus-Aureus-Virulence-Factors.aspx

  These interactions not only facilitate colonization but also promote immune evasion by inducing clot formation or platelet aggregation. […] Once established, S. aureus produces an extensive range of toxins and enzymes that enable it to invade tissues, evade immune responses, and extract nutrients. […] The bacterium also secretes exoproteins, including nucleases, proteases, lipases, hyaluronidase, and collagenase, which break down host tissues into usable nutrients. […] Additional virulence factors include exfoliative toxins A and B (ETA and ETB), which disrupt skin integrity, and EDIN exotoxins, which facilitate tissue invasion. […] Enterotoxins such as SEA, SEB, and SECn, along with toxic shock syndrome toxin-1 (TSST-1), act as superantigens, triggering uncontrolled immune activation, high fevers, and potentially fatal systemic inflammation.

• #19 The role of Staphylococcus aureus quorum sensing in cutaneous and systemic infections | Inflammation and Regeneration | Full Text

  https://inflammregen.biomedcentral.com/articles/10.1186/s41232-024-00323-8

  Staphylococcus aureus is a leading cause of human bacterial infections worldwide. It is the most common causative agent of skin and soft tissue infections, and can also cause various other infections, including pneumonia, osteomyelitis, as well as life-threatening infections, such as sepsis and infective endocarditis. […] Agr functions as a central quorum sensing (QS) system in S. aureus, allowing bacteria to adjust gene expression in response to population density. Depending on Agr expression, S. aureus secretes various toxins, contributing to virulence in infectious diseases. […] The pathophysiology of S. aureus infection is substantially influenced by phenotypic changes resulting from factors beyond Agr. […] The quorum sensing (QS) system is the ability of bacteria to adjust gene expressions in response to their population density.

• #20 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Staphylococcus-Aureus-Virulence-Factors.aspx

  The virulence of S. aureus lies in its ability to adapt to environmental pressures and immune defenses quickly. A central feature of its survival strategy is the accessory gene regulatory (Agr) two-component system (TCS), which helps control the production of key virulence factors. […] When bacterial populations increase within host tissues, the Agr system is activated, triggering toxin production. As the infection progresses, Agr activity is downregulated, helping the bacteria evade immune detection. […] One of its key toxins, -toxin, compromises epithelial barriers by activating the metalloproteinase ADAM10, which disrupts cell junctions. […] To adhere to host tissues, S. aureus uses surface proteins from the MSCRAMM family such as staphylococcal protein A (SpA), fibronectin-binding proteins (FnbpA/B), and clumping factors (ClfA/B) which bind to components like collagen and fibrinogen.

• #21 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Staphylococcus-Aureus-Virulence-Factors.aspx

  The virulence of S. aureus lies in its ability to adapt to environmental pressures and immune defenses quickly. A central feature of its survival strategy is the accessory gene regulatory (Agr) two-component system (TCS), which helps control the production of key virulence factors. […] When bacterial populations increase within host tissues, the Agr system is activated, triggering toxin production. As the infection progresses, Agr activity is downregulated, helping the bacteria evade immune detection. […] One of its key toxins, -toxin, compromises epithelial barriers by activating the metalloproteinase ADAM10, which disrupts cell junctions. […] To adhere to host tissues, S. aureus uses surface proteins from the MSCRAMM family such as staphylococcal protein A (SpA), fibronectin-binding proteins (FnbpA/B), and clumping factors (ClfA/B) which bind to components like collagen and fibrinogen.

• #22 Molecular Pathogenesis of Staphylococcus aureus Infection

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2919328/

  S. aureus has evolved a comprehensive strategy to address the challenges posed by the human immune system. […] The emergence of community-associated methicillin-resistant S. aureus (CA-MRSA) infections in individuals with no predisposing conditions suggests an increased pathogenicity of the bacterium, which may be related to acquisition of novel genetic elements. […] Here, I review the various strategies used by S. aureus to evade obstacles laid out by the human host during colonization and infection. […] S. aureus has an extraordinary repertoire of virulence factors that allows it to survive extreme conditions within the human host. […] The past ten years however have witnessed the emergence of new clones of MRSA that have rapidly spread across continents, causing rampant skin and soft tissue infections and some unusually severe diseases.

• #23 Molecular Pathogenesis of Staphylococcus aureus Infection

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2919328/

  This review is written with clinician scientists as the target audience. […] To impart a better appreciation of MRSA pathogenesis, I will first describe the obstacles S. aureus needs to overcome to establish an infection, then highlight aspects of pathogenesis that are unique to healthcare-associated MRSA (HA-MRSA) and CA-MRSA. […] For S. aureus, colonization of the human nose presents a significant challenge that requires not only adherence to nasal epithelial cells, but also an ability to cope with host defense and competing resident microorganisms. […] S. aureus adheres and invades host epithelial cells using a variety of molecules that are collectively termed MSCRAMM (Microbial surface components recognizing adhesive matrix molecules). […] Host immune deterrents for bacterial nasal colonization include antimicrobial peptides, lysozyme, lactoferrin, and IgA.

• #24 Molecular Pathogenesis of Staphylococcus aureus Infection

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2919328/

  This review is written with clinician scientists as the target audience. […] To impart a better appreciation of MRSA pathogenesis, I will first describe the obstacles S. aureus needs to overcome to establish an infection, then highlight aspects of pathogenesis that are unique to healthcare-associated MRSA (HA-MRSA) and CA-MRSA. […] For S. aureus, colonization of the human nose presents a significant challenge that requires not only adherence to nasal epithelial cells, but also an ability to cope with host defense and competing resident microorganisms. […] S. aureus adheres and invades host epithelial cells using a variety of molecules that are collectively termed MSCRAMM (Microbial surface components recognizing adhesive matrix molecules). […] Host immune deterrents for bacterial nasal colonization include antimicrobial peptides, lysozyme, lactoferrin, and IgA.

• #25 Molecular Pathogenesis of Staphylococcus aureus Infection

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2919328/

  This review is written with clinician scientists as the target audience. […] To impart a better appreciation of MRSA pathogenesis, I will first describe the obstacles S. aureus needs to overcome to establish an infection, then highlight aspects of pathogenesis that are unique to healthcare-associated MRSA (HA-MRSA) and CA-MRSA. […] For S. aureus, colonization of the human nose presents a significant challenge that requires not only adherence to nasal epithelial cells, but also an ability to cope with host defense and competing resident microorganisms. […] S. aureus adheres and invades host epithelial cells using a variety of molecules that are collectively termed MSCRAMM (Microbial surface components recognizing adhesive matrix molecules). […] Host immune deterrents for bacterial nasal colonization include antimicrobial peptides, lysozyme, lactoferrin, and IgA.

• #26 Staphylococcus aureus – Wikipedia

  https://en.wikipedia.org/wiki/Staphylococcus_aureus

  Staphylococcus aureus biofilm is the predominant cause of orthopedic implant-related infections, but is also found on cardiac implants, vascular grafts, various catheters, and cosmetic surgical implants. […] Once the device becomes infected, it must be completely removed, since S. aureus biofilm cannot be destroyed by antibiotic treatments. […] Current therapy for S. aureus biofilm-mediated infections involves surgical removal of the infected device followed by antibiotic treatment. […] These agents have shown inhibitory effects against S. aureus embedded in biofilms. […] Staphylococcus aureus produces various enzymes such as coagulase (bound and free coagulases) which facilitates the conversion of fibrinogen to fibrin to cause clots which is important in skin infections.

• #27 Molecular Pathogenesis of Staphylococcus aureus Infection

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2919328/

  Once colonization is established, S. aureus is positioned in close proximity to the throat, ears, mouth and sinus; yet, surprisingly nasal carriage rarely leads to overt infection of these sites. […] Initial exposure of S. aureus to host tissues beyond the mucosal surface or skin is thought to trigger upregulation of virulence genes. […] S. aureus has been generally recognized to survive well both inside and outside of host cells. […] S. aureus avoids opsonophagocytosis by expressing on its surface a capsule, clumping factor A, protein A, and a number of complement inhibitors, all of which inactivate or prevent host opsonins from binding or targeting the bacterium for destruction. […] S. aureus can shelter within epithelial cells, endothelial cells, and even macrophages. […] S. aureus deploys a number of strategies to resist neutrophil killing.

• #28 Staphylococcus Aureus Infection: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/971358-overview

  The organism may cause disease through tissue invasion and toxin production. The toxins liberated by the organism may have effects at sites distant from the focus of infection or colonization. […] The postulated sequence of events that leads to infection is initiated with carriage of the organism. The organism is then disseminated via hand carriage to body sites where infection may occur (either through overt breaks in dermal surfaces, such as vascular catheterization or operative incisions, or through less evident breakdown in barrier function, such as eczema or shaving-associated microtrauma). […] The hallmark of staphylococcal infection is the abscess, which consists of a fibrin wall surrounded by inflamed tissues enclosing a central core of pus containing organisms and leukocytes. From this focus of infection, the organisms may be disseminated hematogenously, even from the smallest abscess. The ability to elaborate proteolytic enzymes facilitates the process. This may result in pneumonia, bone and joint infection, and infection of the heart valves. In immunocompromised hosts (eg, patients with cancer who are neutropenic and have a central venous line), 20-30% develop serious complications or fatal sepsis following catheter-related S aureus bacteremia.

• #29 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Staphylococcus-Aureus-Virulence-Factors.aspx

  These interactions not only facilitate colonization but also promote immune evasion by inducing clot formation or platelet aggregation. […] Once established, S. aureus produces an extensive range of toxins and enzymes that enable it to invade tissues, evade immune responses, and extract nutrients. […] The bacterium also secretes exoproteins, including nucleases, proteases, lipases, hyaluronidase, and collagenase, which break down host tissues into usable nutrients. […] Additional virulence factors include exfoliative toxins A and B (ETA and ETB), which disrupt skin integrity, and EDIN exotoxins, which facilitate tissue invasion. […] Enterotoxins such as SEA, SEB, and SECn, along with toxic shock syndrome toxin-1 (TSST-1), act as superantigens, triggering uncontrolled immune activation, high fevers, and potentially fatal systemic inflammation.

• #30 Staphylococcus Aureus Infection: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/971358-overview

  The organism may cause disease through tissue invasion and toxin production. The toxins liberated by the organism may have effects at sites distant from the focus of infection or colonization. […] The postulated sequence of events that leads to infection is initiated with carriage of the organism. The organism is then disseminated via hand carriage to body sites where infection may occur (either through overt breaks in dermal surfaces, such as vascular catheterization or operative incisions, or through less evident breakdown in barrier function, such as eczema or shaving-associated microtrauma). […] The hallmark of staphylococcal infection is the abscess, which consists of a fibrin wall surrounded by inflamed tissues enclosing a central core of pus containing organisms and leukocytes. From this focus of infection, the organisms may be disseminated hematogenously, even from the smallest abscess. The ability to elaborate proteolytic enzymes facilitates the process. This may result in pneumonia, bone and joint infection, and infection of the heart valves. In immunocompromised hosts (eg, patients with cancer who are neutropenic and have a central venous line), 20-30% develop serious complications or fatal sepsis following catheter-related S aureus bacteremia.

• #31 Staphylococcus Aureus Infection: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/971358-overview

  The organism may cause disease through tissue invasion and toxin production. The toxins liberated by the organism may have effects at sites distant from the focus of infection or colonization. […] The postulated sequence of events that leads to infection is initiated with carriage of the organism. The organism is then disseminated via hand carriage to body sites where infection may occur (either through overt breaks in dermal surfaces, such as vascular catheterization or operative incisions, or through less evident breakdown in barrier function, such as eczema or shaving-associated microtrauma). […] The hallmark of staphylococcal infection is the abscess, which consists of a fibrin wall surrounded by inflamed tissues enclosing a central core of pus containing organisms and leukocytes. From this focus of infection, the organisms may be disseminated hematogenously, even from the smallest abscess. The ability to elaborate proteolytic enzymes facilitates the process. This may result in pneumonia, bone and joint infection, and infection of the heart valves. In immunocompromised hosts (eg, patients with cancer who are neutropenic and have a central venous line), 20-30% develop serious complications or fatal sepsis following catheter-related S aureus bacteremia.

• #32 Molecular Pathogenesis of Staphylococcus aureus Infection

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2919328/

  Once colonization is established, S. aureus is positioned in close proximity to the throat, ears, mouth and sinus; yet, surprisingly nasal carriage rarely leads to overt infection of these sites. […] Initial exposure of S. aureus to host tissues beyond the mucosal surface or skin is thought to trigger upregulation of virulence genes. […] S. aureus has been generally recognized to survive well both inside and outside of host cells. […] S. aureus avoids opsonophagocytosis by expressing on its surface a capsule, clumping factor A, protein A, and a number of complement inhibitors, all of which inactivate or prevent host opsonins from binding or targeting the bacterium for destruction. […] S. aureus can shelter within epithelial cells, endothelial cells, and even macrophages. […] S. aureus deploys a number of strategies to resist neutrophil killing.

• #33 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Staphylococcus-Aureus-Virulence-Factors.aspx

  S. aureus excels at evading the immune system. It often escapes from the bloodstream into tissues, where it forms abscesses dense bacterial clusters surrounded by immune cells that it effectively traps outside. […] The bacterium interferes with neutrophil function at multiple levels: it prevents their migration, suppresses their activation, and neutralizes their killing mechanisms. […] Enzymes such as superoxide dismutase (SOD), staphyloxanthin, and SPIN protect the bacterium from reactive oxygen species, while nucleases break down neutrophil extracellular traps (NETs). […] Immune shielding is further enhanced by biofilm formation, protective capsules, and cloaking within fibrin clots. […] Leukocidins, including Panton-Valentine leukocidin (PVL), are especially dangerous, as they destroy white blood cells even at low concentrations. […] Beyond antibody evasion, S. aureus also induces anti-inflammatory responses and adaptive immune tolerance, further complicating the hosts ability to eliminate the infection.

• #34 Immune System Evasion Mechanisms in Staphylococcus aureus: Current Understanding – Journal of Pure and Applied Microbiology

  https://microbiologyjournal.org/immune-system-evasion-mechanisms-in-staphylococcus-aureus-current-understanding/

  It has been shown that S. aureus developed different mechanisms to avoid the action of the complement system by producing a number of proteins that can change and affect the stages of the complement cascade, these mechanisms include; preventing complement identification; cleavage of complement proteins; and/or inhibit the interaction of complement receptors on phagocytes. […] S. aureus produces many significant factors to avoid and evade from phagocytosis. It expresses anti-opsonic proteins bound to the surface and a capsule of polysaccharides which: (a) interfere with antibodies and with the formation of complement through classical and alternative pathways, (b) inhibit their interaction to neutrophil complement receptor and Fc receptor. […] S. aureus is a common pathogen that has the ability to secrete and produce toxins which contribute to the damage of host cells membranes. The expression of cytolytic toxins that damage leukocytes contributes to development of abscesses by the killing of neutrophils that are attempting to engulf and kill the bacteria. […] It seems clear that S. aureus is a widespread organism that lives as a normal flora in the nose and on the skin of humans and animals. It is a very successful pathogen because of its ability to express and produce virulence factors to evade the recognition and the killing of the host immune cells.

• #35 Molecular Pathogenesis of Staphylococcus aureus Infection

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2919328/

  Once colonization is established, S. aureus is positioned in close proximity to the throat, ears, mouth and sinus; yet, surprisingly nasal carriage rarely leads to overt infection of these sites. […] Initial exposure of S. aureus to host tissues beyond the mucosal surface or skin is thought to trigger upregulation of virulence genes. […] S. aureus has been generally recognized to survive well both inside and outside of host cells. […] S. aureus avoids opsonophagocytosis by expressing on its surface a capsule, clumping factor A, protein A, and a number of complement inhibitors, all of which inactivate or prevent host opsonins from binding or targeting the bacterium for destruction. […] S. aureus can shelter within epithelial cells, endothelial cells, and even macrophages. […] S. aureus deploys a number of strategies to resist neutrophil killing.

• #36 Immune System Evasion Mechanisms in Staphylococcus aureus: Current Understanding – Journal of Pure and Applied Microbiology

  https://microbiologyjournal.org/immune-system-evasion-mechanisms-in-staphylococcus-aureus-current-understanding/

  It has been shown that S. aureus developed different mechanisms to avoid the action of the complement system by producing a number of proteins that can change and affect the stages of the complement cascade, these mechanisms include; preventing complement identification; cleavage of complement proteins; and/or inhibit the interaction of complement receptors on phagocytes. […] S. aureus produces many significant factors to avoid and evade from phagocytosis. It expresses anti-opsonic proteins bound to the surface and a capsule of polysaccharides which: (a) interfere with antibodies and with the formation of complement through classical and alternative pathways, (b) inhibit their interaction to neutrophil complement receptor and Fc receptor. […] S. aureus is a common pathogen that has the ability to secrete and produce toxins which contribute to the damage of host cells membranes. The expression of cytolytic toxins that damage leukocytes contributes to development of abscesses by the killing of neutrophils that are attempting to engulf and kill the bacteria. […] It seems clear that S. aureus is a widespread organism that lives as a normal flora in the nose and on the skin of humans and animals. It is a very successful pathogen because of its ability to express and produce virulence factors to evade the recognition and the killing of the host immune cells.

• #37 Molecular Pathogenesis of Staphylococcus aureus Infection

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2919328/

  Once colonization is established, S. aureus is positioned in close proximity to the throat, ears, mouth and sinus; yet, surprisingly nasal carriage rarely leads to overt infection of these sites. […] Initial exposure of S. aureus to host tissues beyond the mucosal surface or skin is thought to trigger upregulation of virulence genes. […] S. aureus has been generally recognized to survive well both inside and outside of host cells. […] S. aureus avoids opsonophagocytosis by expressing on its surface a capsule, clumping factor A, protein A, and a number of complement inhibitors, all of which inactivate or prevent host opsonins from binding or targeting the bacterium for destruction. […] S. aureus can shelter within epithelial cells, endothelial cells, and even macrophages. […] S. aureus deploys a number of strategies to resist neutrophil killing.

• #38 Staphylococcus Aureus Infection: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/971358-overview

  Persistent deep-seated infections have now been linked to small-colony variants of the organism. This population is more resistant to antibiotics and grows slowly. These organisms have been described in patients with cystic fibrosis and may contribute to the persistence of S aureus in these patients. […] The organism also elaborates toxins that can cause specific diseases or syndromes and likely participate in the pathogenesis of staphylococcal infection. Enterotoxin-producing strains of S aureus cause one of the most common food-borne illnesses. […] The most feared manifestation of S aureus toxin production is toxic shock syndrome (TSS). Although first described in children, it was most frequently associated with women using tampons during menstruation. […] The syndrome is associated with strains that produce the exotoxin TSST-1, but strains that produce enterotoxins B and C may cause 50% of cases of nonmenstrual TSS. These toxins are superantigens, T-cell mitogens that bind directly to invariant regions of major histocompatibility complex class II molecules, causing an expansion of clonal T cells, followed by a massive release of cytokines. This cytokine release mediates the TSS; the resultant pathophysiology mimics that of endotoxic shock.

• #39 Molecular Pathogenesis of Staphylococcus aureus Infection

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2919328/

  Once colonization is established, S. aureus is positioned in close proximity to the throat, ears, mouth and sinus; yet, surprisingly nasal carriage rarely leads to overt infection of these sites. […] Initial exposure of S. aureus to host tissues beyond the mucosal surface or skin is thought to trigger upregulation of virulence genes. […] S. aureus has been generally recognized to survive well both inside and outside of host cells. […] S. aureus avoids opsonophagocytosis by expressing on its surface a capsule, clumping factor A, protein A, and a number of complement inhibitors, all of which inactivate or prevent host opsonins from binding or targeting the bacterium for destruction. […] S. aureus can shelter within epithelial cells, endothelial cells, and even macrophages. […] S. aureus deploys a number of strategies to resist neutrophil killing.

• #40 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Staphylococcus-Aureus-Virulence-Factors.aspx

  S. aureus excels at evading the immune system. It often escapes from the bloodstream into tissues, where it forms abscesses dense bacterial clusters surrounded by immune cells that it effectively traps outside. […] The bacterium interferes with neutrophil function at multiple levels: it prevents their migration, suppresses their activation, and neutralizes their killing mechanisms. […] Enzymes such as superoxide dismutase (SOD), staphyloxanthin, and SPIN protect the bacterium from reactive oxygen species, while nucleases break down neutrophil extracellular traps (NETs). […] Immune shielding is further enhanced by biofilm formation, protective capsules, and cloaking within fibrin clots. […] Leukocidins, including Panton-Valentine leukocidin (PVL), are especially dangerous, as they destroy white blood cells even at low concentrations. […] Beyond antibody evasion, S. aureus also induces anti-inflammatory responses and adaptive immune tolerance, further complicating the hosts ability to eliminate the infection.

• #41 The Human Immune System toward Staphylococcus aureus

  https://www.openmicrobiologyjournal.com/VOLUME/14/PAGE/164/FULLTEXT/

  Nevertheless, S. aureus cells can destroy NET, and the degradation product 2-deoxyadenosine that stimulates apoptosis in macrophage cells, which raise bacterial survival in the abscess. […] The significance of antibody-mediated protection toward microbial infectious agents is found by demonstrating this event that the absence of B lymphocyte maturation causes susceptibility against infections with encapsulated bacteria and viruses. […] The notable absence of raised susceptibility in this regard to S. aureus argues that antibody is un-significant in protection toward infection of S. aureus. […] Nevertheless, it has found that early cutaneous S. aureus infection could stimulate antibody-mediated support toward a subsequent microbial infection in certain mouse strains. […] T lymphocyte has a dual function: (1) it is important for the production of opposing antibodies because T cell is essential for maturation of antibody affinity as well as class switches, (2) T cells promote phagocytosis by absorbing neutrophils and macrophages from the bone marrow to the site of infection.

• #42 Staphylococcus aureus bacteria turns immune system against itself | University of Chicago News

  https://news.uchicago.edu/story/staphylococcus-aureus-bacteria-turns-immune-system-against-itself

  They discovered that S. aureus were converting NETs into 2-deoxyadenosine (dAdo), a molecule that is toxic to macrophages. This effectively turned NETs into a weapon against the immune system. […] Our work describes for the first time the mechanism that these bacteria use to exclude macrophages from infected sites, Schneewind said. Coupled with previously known mechanisms that suppress the adaptive immune response, the success of these organisms is almost guaranteed. […] But both genes and the dAdo molecule are closely related to important human physiological mechanisms, and Schneewind believes targeting these in bacteria, without harming human function, could be difficult.

• #43 Staphylococcus Aureus Infection: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/971358-overview

  Persistent deep-seated infections have now been linked to small-colony variants of the organism. This population is more resistant to antibiotics and grows slowly. These organisms have been described in patients with cystic fibrosis and may contribute to the persistence of S aureus in these patients. […] The organism also elaborates toxins that can cause specific diseases or syndromes and likely participate in the pathogenesis of staphylococcal infection. Enterotoxin-producing strains of S aureus cause one of the most common food-borne illnesses. […] The most feared manifestation of S aureus toxin production is toxic shock syndrome (TSS). Although first described in children, it was most frequently associated with women using tampons during menstruation. […] The syndrome is associated with strains that produce the exotoxin TSST-1, but strains that produce enterotoxins B and C may cause 50% of cases of nonmenstrual TSS. These toxins are superantigens, T-cell mitogens that bind directly to invariant regions of major histocompatibility complex class II molecules, causing an expansion of clonal T cells, followed by a massive release of cytokines. This cytokine release mediates the TSS; the resultant pathophysiology mimics that of endotoxic shock.

• #44 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Staphylococcus-Aureus-Virulence-Factors.aspx

  S. aureus excels at evading the immune system. It often escapes from the bloodstream into tissues, where it forms abscesses dense bacterial clusters surrounded by immune cells that it effectively traps outside. […] The bacterium interferes with neutrophil function at multiple levels: it prevents their migration, suppresses their activation, and neutralizes their killing mechanisms. […] Enzymes such as superoxide dismutase (SOD), staphyloxanthin, and SPIN protect the bacterium from reactive oxygen species, while nucleases break down neutrophil extracellular traps (NETs). […] Immune shielding is further enhanced by biofilm formation, protective capsules, and cloaking within fibrin clots. […] Leukocidins, including Panton-Valentine leukocidin (PVL), are especially dangerous, as they destroy white blood cells even at low concentrations. […] Beyond antibody evasion, S. aureus also induces anti-inflammatory responses and adaptive immune tolerance, further complicating the hosts ability to eliminate the infection.

• #45 Staphylococcus – Medical Microbiology – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK8448/

  Staphylococci can cause many forms of infection. (1) S aureus causes superficial skin lesions (boils, styes) and localized abscesses in other sites. (2) S aureus causes deep-seated infections, such as osteomyelitis and endocarditis and more serious skin infections (furunculosis). (3) S aureus is a major cause of hospital acquired (nosocomial) infection of surgical wounds and, with S epidermidis, causes infections associated with indwelling medical devices. (4) S aureus causes food poisoning by releasing enterotoxins into food. (5) S aureus causes toxic shock syndrome by release of superantigens into the blood stream. (6) S saprophiticus causes urinary tract infections, especially in girls. (7) Other species of staphylococci (S lugdunensis, S haemolyticus, S warneri, S schleiferi, S intermedius) are infrequent pathogens.

• #46 Skin Infections Caused by Staphylococcus aureus | HTML | Acta Dermato-Venereologica

  https://www.medicaljournals.se/acta/content/html/10.2340/00015555-3466

  Staphylococcus aureus is the most common pathogen involved in skin infections worldwide, regardless of the patients age, the climate or geographical area. The main skin clinical manifestations can be linked to a few toxins produced by the bacteria, which give rise to a rich and varied clinical spectrum. Panton Valentine leucocidin, exfoliatins, enterotoxins and toxin shock syndrome toxin 1 are the main toxins involved in most dermatological manifestations associated with S. aureus. […] The pathophysiology of staphylococcal impetigo is related to the local production of exfoliatin toxins A and B. The target protein of exfoliatins A and B is desmoglein 1, a desmosomal protein whose role is the cohesion between keratinocytes, and it is mainly located in the most superficial layer of the epidermis. The main consequence of the action of the toxin on desmoglein 1 is rupture of keratinocyte cohesion and formation of a bullae.

• #47 Skin Infections Caused by Staphylococcus aureus | HTML | Acta Dermato-Venereologica

  https://www.medicaljournals.se/acta/content/html/10.2340/00015555-3466

  A circular desquamative flange may surround the necrotic centre. In recent years it has been found that up to 90% of the S. aureus, isolated from furuncles in some areas produce PVL virulence factor. This leucocidin leads to local destruction of leucocytes with the formation of larger skin lesions, which respond less well to treatment and tend to recur; the organisms can also cause suppurative pneumonia. […] The epidemiology of MRSA has entered a new era the last 25 years. MRSA with new characteristics have emerged in the community setting, namely outside of healthcare facilities. […] Almost all of CA-MRSA, including the major clones, produce the PVL toxin, which explains the predominance of suppurative skin infections as clinical presentations of CA-MRSA infections.

• #48 Staphylococcus aureus-Epidemiology, Pathogenesis & Treatment

  https://microbiologynotes.org/staphylococcus-aureus-epidemiology-pathogenesis-treatment/

  The exfoliative toxin, cause blister-like epidermal separation, localized at the skin region. […] In Staphylococcal scalded skin syndrome, it is caused by a toxin, by which epithelial desquamation occurs. […] In Staphylococcal, TSS (Toxic Shock Syndrome), is a pyrogenic exotoxin TSST-1, which stimulates the release of superantigen-mediated cytokine.

• #49

  https://link.springer.com/article/10.1007/s00281-011-0291-7

  Staphylococcus aureus is a common human pathogen highly evolved as both a component of the commensal flora and as a major cause of invasive infection. […] The ability of S. aureus to adapt to the milieu of the respiratory tract has facilitated its emergence as a respiratory pathogen. […] The expression of surface adhesins facilitates its persistence in the airways. […] In addition, the highly sophisticated interactions of the multiple S. aureus virulence factors, particularly the -hemolysin and protein A, with diverse immune effectors in the lung such as ADAM10, TNFR1, EGFR, immunoglobulin, and complement all contribute to the pathogenesis of staphylococcal pneumonia.

• #50 Clinical and molecular aspects of the pathogenesis of Staphylococcus aureus bone and joint infections | Microbiology Society

  https://www.microbiologyresearch.org/content/journal/jmm/10.1099/00222615-44-3-157

  Staphylococcus aureus is an important cause of bone and joint infections. […] S. aureus produces a number of extracellular and cell-associated factors, but it is unclear what role these have as virulence factors in vivo. […] Surface factors which may be important in pathogenesis include the cell wall (activates complement and stimulates cytokine release), capsular polysaccharide (promotes adhesion to host cell surfaces), collagen receptors and fibronectin-binding protein. […] Staphylococcal toxic shock syndrome toxin (TSST-1) and the enterotoxins are super-antigens and have the potential to suppress plasma cell differentiation and antibody responsiveness. […] There is little evidence supporting a role for coagulase, lipase and the haemolysins in staphylococcal bone and joint infections.

• #51 Staphylococcal Infections: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/228816-overview

  S aureus is a gram-positive coccus that is both catalase- and coagulase-positive. Colonies are golden and strongly hemolytic on blood agar. They produce a range of toxins, including alpha-toxin, beta-toxin, gamma-toxin, delta-toxin, exfoliatin, enterotoxins, Panton-Valentine leukocidin (PVL), and toxic shock syndrome toxin1 (TSST-1). The enterotoxins and TSST-1 are associated with toxic shock syndrome. PVL is associated with necrotic skin and lung infections and has been shown to be a major virulence factor for pneumonia and osteomyelitis. CoNS, particularly S epidermidis, produce an exopolysaccharide (slime) that promotes foreign-body adherence and resistance to phagocytosis. […] Nienaber et al have demonstrated that methicillin-susceptible S aureus (MSSA) isolates causing endocarditis are more likely to be from a specific clonal cluster (CC30) and to possess specific virulence genes as compared to MSSA isolates from the same regions causing soft tissue infection. Isolates from patients with endocarditis were more likely to possess genes for 3 different adhesins and 5 different enterotoxins. The gene for PVL was found in the minority of both groups.

• #52 Staphylococcus aureus – Wikipedia

  https://en.wikipedia.org/wiki/Staphylococcus_aureus

  Staphylococcus aureus biofilm is the predominant cause of orthopedic implant-related infections, but is also found on cardiac implants, vascular grafts, various catheters, and cosmetic surgical implants. […] Once the device becomes infected, it must be completely removed, since S. aureus biofilm cannot be destroyed by antibiotic treatments. […] Current therapy for S. aureus biofilm-mediated infections involves surgical removal of the infected device followed by antibiotic treatment. […] These agents have shown inhibitory effects against S. aureus embedded in biofilms. […] Staphylococcus aureus produces various enzymes such as coagulase (bound and free coagulases) which facilitates the conversion of fibrinogen to fibrin to cause clots which is important in skin infections.

• #53 Staphylococcus – Medical Microbiology – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK8448/

  The best characterized and most potent membrane-damaging toxin of S aureus is -toxin. It is expressed as a monomer that binds to the membrane of susceptible cells. […] The notion that -toxin is a major virulence factor of S aureus is supported by studies with the purified toxin in animals and in organ culture. Also, mutants lacking -toxin are less virulent in a variety of animal infection models. […] S aureus can express two different types of toxin with superantigen activity, enterotoxins, of which there are six serotypes (A, B, C, D, E and G) and toxic shock syndrome toxin (TSST-1). Enterotoxins cause diarrhea and vomiting when ingested and are responsible for staphylococcal food poisoning. When expressed systemically, enterotoxins can cause toxic shock syndrome (TSS) – indeed enterotoxins B and C cause 50% of non-menstrual TSS. TSST-1 is very weakly related to enterotoxins and does not have emetic activity. TSST-1 is responsible for 75% of TSS, including all menstrual cases.

• #54 Staphylococcus Aureus Infection: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/971358-overview

  Persistent deep-seated infections have now been linked to small-colony variants of the organism. This population is more resistant to antibiotics and grows slowly. These organisms have been described in patients with cystic fibrosis and may contribute to the persistence of S aureus in these patients. […] The organism also elaborates toxins that can cause specific diseases or syndromes and likely participate in the pathogenesis of staphylococcal infection. Enterotoxin-producing strains of S aureus cause one of the most common food-borne illnesses. […] The most feared manifestation of S aureus toxin production is toxic shock syndrome (TSS). Although first described in children, it was most frequently associated with women using tampons during menstruation. […] The syndrome is associated with strains that produce the exotoxin TSST-1, but strains that produce enterotoxins B and C may cause 50% of cases of nonmenstrual TSS. These toxins are superantigens, T-cell mitogens that bind directly to invariant regions of major histocompatibility complex class II molecules, causing an expansion of clonal T cells, followed by a massive release of cytokines. This cytokine release mediates the TSS; the resultant pathophysiology mimics that of endotoxic shock.

• #55 Molecular Pathogenesis of Staphylococcus aureus Infection

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2919328/

  MRSA deserves separate consideration in S. aureus pathogenesis because it is associated with distinct epidemiology, particularly morbidity and mortality. […] MRSA can be divided into HA-MRSA and CA-MRSA, two genotypically dissimilar groups of bacteria that target different but overlapping populations and cause different diseases. […] HA-MRSA harbors large staphylococcal chromosome cassettes (SCCmec types I-III), which encode one or multiple antibiotic resistance genes. […] Interestingly, when removed from the healthcare setting, HA-MRSA rarely causes diseases in individuals without predisposing conditions. […] CA-MRSA strains were responsible for a dramatic increase in the incidence of infections, particularly of the skin and soft tissue and were the cause of many unusually severe infections such as necrotizing pneumonia, necrotizing fasciitis, and myositis.

• #56 Methicillin-resistant Staphylococcus aureus – Wikipedia

  https://en.wikipedia.org/wiki/Methicillin-resistant_Staphylococcus_aureus

  Methicillin-resistant Staphylococcus aureus (MRSA) is a group of gram-positive bacteria that are genetically distinct from other strains of Staphylococcus aureus. MRSA is responsible for several difficult-to-treat infections in humans. It caused more than 100,000 deaths worldwide attributable to antimicrobial resistance in 2019. […] MRSA is any strain of S. aureus that has developed (through natural selection) or acquired (through horizontal gene transfer) a multiple drug resistance to beta-lactam antibiotics. […] A defining characteristic of MRSA is its ability to thrive in the presence of penicillin-like antibiotics, which normally prevent bacterial growth by inhibiting the synthesis of cell wall material. This is due to a resistance gene, mecA, which stops -lactam antibiotics from inactivating the enzymes (transpeptidases) critical for cell wall synthesis.

• #57 Methicillin-resistant Staphylococcus aureus – Wikipedia

  https://en.wikipedia.org/wiki/Methicillin-resistant_Staphylococcus_aureus

  Staphylococcal cassette chromosome mec (SCCmec) is a genomic island of unknown origin containing the antibiotic resistance gene mecA. […] Different SCCmec genotypes confer different microbiological characteristics, such as different antimicrobial resistance rates. […] These distinctions were thoroughly investigated by Collins et al. in 2001, and can be explained by the fitness differences associated with the carriage of a large or small SCCmec plasmid. […] mecA is a biomarker gene responsible for resistance to methicillin and other -lactam antibiotics. […] mecA encodes penicillin-binding protein 2a (PBP2a), which differs from other penicillin-binding proteins as its active site does not bind methicillin or other -lactam antibiotics. […] The arginine catabolic mobile element (ACME) is a virulence factor present in many MRSA strains but not prevalent in MSSA.

• #58 Methicillin-resistant Staphylococcus aureus – Wikipedia

  https://en.wikipedia.org/wiki/Methicillin-resistant_Staphylococcus_aureus

  Staphylococcal cassette chromosome mec (SCCmec) is a genomic island of unknown origin containing the antibiotic resistance gene mecA. […] Different SCCmec genotypes confer different microbiological characteristics, such as different antimicrobial resistance rates. […] These distinctions were thoroughly investigated by Collins et al. in 2001, and can be explained by the fitness differences associated with the carriage of a large or small SCCmec plasmid. […] mecA is a biomarker gene responsible for resistance to methicillin and other -lactam antibiotics. […] mecA encodes penicillin-binding protein 2a (PBP2a), which differs from other penicillin-binding proteins as its active site does not bind methicillin or other -lactam antibiotics. […] The arginine catabolic mobile element (ACME) is a virulence factor present in many MRSA strains but not prevalent in MSSA.

• #59 Molecular Pathogenesis of Staphylococcus aureus Infection

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2919328/

  MRSA deserves separate consideration in S. aureus pathogenesis because it is associated with distinct epidemiology, particularly morbidity and mortality. […] MRSA can be divided into HA-MRSA and CA-MRSA, two genotypically dissimilar groups of bacteria that target different but overlapping populations and cause different diseases. […] HA-MRSA harbors large staphylococcal chromosome cassettes (SCCmec types I-III), which encode one or multiple antibiotic resistance genes. […] Interestingly, when removed from the healthcare setting, HA-MRSA rarely causes diseases in individuals without predisposing conditions. […] CA-MRSA strains were responsible for a dramatic increase in the incidence of infections, particularly of the skin and soft tissue and were the cause of many unusually severe infections such as necrotizing pneumonia, necrotizing fasciitis, and myositis.

• #60 Molecular Pathogenesis of Staphylococcus aureus Infection

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2919328/

  MRSA deserves separate consideration in S. aureus pathogenesis because it is associated with distinct epidemiology, particularly morbidity and mortality. […] MRSA can be divided into HA-MRSA and CA-MRSA, two genotypically dissimilar groups of bacteria that target different but overlapping populations and cause different diseases. […] HA-MRSA harbors large staphylococcal chromosome cassettes (SCCmec types I-III), which encode one or multiple antibiotic resistance genes. […] Interestingly, when removed from the healthcare setting, HA-MRSA rarely causes diseases in individuals without predisposing conditions. […] CA-MRSA strains were responsible for a dramatic increase in the incidence of infections, particularly of the skin and soft tissue and were the cause of many unusually severe infections such as necrotizing pneumonia, necrotizing fasciitis, and myositis.

• #61 Molecular Pathogenesis of Staphylococcus aureus Infection | Pediatric Research

  https://www.nature.com/articles/pr2009125

  Interestingly, when removed from the healthcare setting, HA-MRSA rarely causes diseases in individuals without predisposing conditions. […] It has therefore been suggested that HA-MRSA represents less robust strains of S. aureus that could only survive environments where bacterial competition is limited by antibiotic pressure. […] As physicians attempt to grapple with the antibiotic resistance problem posed by HA-MRSA, increasingly there are reports of the more virulent CA-MRSA infiltrating the healthcare setting. […] CA-MRSA strains were responsible for a dramatic increase in the incidence of infections, particularly of the skin and soft tissue and were the cause of many unusually severe infections such as necrotizing pneumonia, necrotizing fasciitis, and myositis. […] The epidemiologic findings, though suggestive of a more virulent phenotype, need to be interpreted with caution.

• #62 Molecular Pathogenesis of Staphylococcus aureus Infection | Pediatric Research

  https://www.nature.com/articles/pr2009125

  Interestingly, when removed from the healthcare setting, HA-MRSA rarely causes diseases in individuals without predisposing conditions. […] It has therefore been suggested that HA-MRSA represents less robust strains of S. aureus that could only survive environments where bacterial competition is limited by antibiotic pressure. […] As physicians attempt to grapple with the antibiotic resistance problem posed by HA-MRSA, increasingly there are reports of the more virulent CA-MRSA infiltrating the healthcare setting. […] CA-MRSA strains were responsible for a dramatic increase in the incidence of infections, particularly of the skin and soft tissue and were the cause of many unusually severe infections such as necrotizing pneumonia, necrotizing fasciitis, and myositis. […] The epidemiologic findings, though suggestive of a more virulent phenotype, need to be interpreted with caution.

• #63

  https://www.jci.org/articles/view/38226

  Staphylococcus aureus is the leading cause of bacterial infections in developed countries and produces a wide spectrum of diseases, ranging from minor skin infections to fatal necrotizing pneumonia. […] Methicillin-resistant S. aureus (MRSA) was endemic in hospitals by the late 1960s, but it appeared rapidly and unexpectedly in communities in the 1990s and is now prevalent worldwide. […] This Review focuses on progress made toward understanding the success of community-associated MRSA as a human pathogen, with an emphasis on genome-wide approaches and virulence determinants. […] The rapid emergence of community-associated MRSA (CA-MRSA) infections (i.e., those that occur outside of health care facilities in otherwise healthy people) is one of the most surprising events in infectious diseases in recent years.

• #64 Molecular Pathogenesis of Staphylococcus aureus Infection

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2919328/

  MRSA deserves separate consideration in S. aureus pathogenesis because it is associated with distinct epidemiology, particularly morbidity and mortality. […] MRSA can be divided into HA-MRSA and CA-MRSA, two genotypically dissimilar groups of bacteria that target different but overlapping populations and cause different diseases. […] HA-MRSA harbors large staphylococcal chromosome cassettes (SCCmec types I-III), which encode one or multiple antibiotic resistance genes. […] Interestingly, when removed from the healthcare setting, HA-MRSA rarely causes diseases in individuals without predisposing conditions. […] CA-MRSA strains were responsible for a dramatic increase in the incidence of infections, particularly of the skin and soft tissue and were the cause of many unusually severe infections such as necrotizing pneumonia, necrotizing fasciitis, and myositis.

• #65 Molecular Pathogenesis of Staphylococcus aureus Infection | Pediatric Research

  https://www.nature.com/articles/pr2009125

  S. aureus has evolved a comprehensive strategy to address the challenges posed by the human immune system. […] The emergence of community-associated methicillin-resistant S. aureus (CA-MRSA) infections in individuals with no predisposing conditions suggests an increased pathogenicity of the bacterium, which may be related to acquisition of novel genetic elements. […] Here, the various strategies used by S. aureus to evade obstacles laid out by the human host during colonization and infection were reviewed. […] The past 10 y however have witnessed the emergence of new clones of MRSA that have rapidly spread across continents, causing rampant skin and soft tissue infections and some unusually severe diseases. […] Unlike traditional MRSA clones which are largely confined to healthcare settings and prey on immunocompromised hosts or hosts with predisposing factors, these community-associated methicillin-resistant S. aureus (CA-MRSA) clones infect previously healthy hosts, particularly children, young and middle-aged adults.

• #66

  https://www.jci.org/articles/view/38226

  CA-MRSA strains can cause severe or fatal disease. […] In this Review, we discuss key components of the recent emergence of CA-MRSA, including transmission and virulence, and we highlight some of the genome-wide approaches used to understand the success of this pathogen. […] The success of S. aureus as a human pathogen depends largely on its ability to circumvent destruction by neutrophils. […] Compared with representative health care-associated MRSA strains, CA-MRSA strains have substantially enhanced ability to evade killing by human neutrophils. […] Thus, there is little doubt that the most prominent CA-MRSA strains are more virulent than traditional health care-associated MRSA strains. […] The ability of S. aureus to produce molecules cytolytic for leukocytes has been known for more than a century.

• #67 The role of Staphylococcus aureus quorum sensing in cutaneous and systemic infections | Inflammation and Regeneration | Full Text

  https://inflammregen.biomedcentral.com/articles/10.1186/s41232-024-00323-8

  The predominant factors of enhanced virulence in CA-MRSA was initially believed to rely on the bacterial ability to evade phagocytes killing by Panton-Valentine leukocidin (PVL), a pore-forming toxin to kill immune cells. However, more recent research have questioned the importance of PVL as a major contributor to CA-MRSA virulence since an increasing number of CA-MRSA clones do not contain lukSF genes responsible for PVL. […] Agr plays a key role in CA-MRSA SSTI in vivo. […] Agr plays a critical role in S. aureus sepsis by facilitating bacterial survival inside phagocytes and even using phagocytes as carriers for dissemination.

• #68

  https://www.jci.org/articles/view/38226

  The role of PVL in the emergence of CA-MRSA is hotly debated, and the relative contribution of PVL to severe invasive CA-MRSA syndromes remains to be determined. […] Data therefore suggest that if PVL contributes to CA-MRSA pathogenesis in humans, its overall role is relatively minor. […] ACME contains genes encoding a complete arginine deiminase pathway; these genes are within an arc cluster and an oligopeptide permease operon. […] Collectively, these findings indicate that ACME has contributed to the success (and perhaps to the emergence) of the epidemic USA300 clone.

• #69 The role of Staphylococcus aureus quorum sensing in cutaneous and systemic infections | Inflammation and Regeneration | Full Text

  https://inflammregen.biomedcentral.com/articles/10.1186/s41232-024-00323-8

  S. aureus possesses an auto-regulatory operon, Agr system, as a QS function. […] When AIP reaches the threshold, the transmembrane receptor on the cell surface, AgrC, is activated via autophosphorylation of its histidine protein kinase (HPK) domain. […] The P3 promoter regulates various toxins via RNAIII, a large regulatory RNA which has a complex secondary structure with several C-rich hairpin loops to interact with its target mRNAs. […] The essential virulence of PSM peptides rely on its cytolytic property, although not all PSMs from S. aureus are cytolytic. […] -Toxin or -hemolysin (hla) is a pore-forming toxin secreted as a soluble monomer. […] -Toxin contributes to the host lethal outcome in bloodstream infections through disseminated thrombosis caused by platelets and neutrophil intoxication.

• #70 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Staphylococcus-Aureus-Virulence-Factors.aspx

  The virulence of S. aureus lies in its ability to adapt to environmental pressures and immune defenses quickly. A central feature of its survival strategy is the accessory gene regulatory (Agr) two-component system (TCS), which helps control the production of key virulence factors. […] When bacterial populations increase within host tissues, the Agr system is activated, triggering toxin production. As the infection progresses, Agr activity is downregulated, helping the bacteria evade immune detection. […] One of its key toxins, -toxin, compromises epithelial barriers by activating the metalloproteinase ADAM10, which disrupts cell junctions. […] To adhere to host tissues, S. aureus uses surface proteins from the MSCRAMM family such as staphylococcal protein A (SpA), fibronectin-binding proteins (FnbpA/B), and clumping factors (ClfA/B) which bind to components like collagen and fibrinogen.

• #71 The Human Immune System toward Staphylococcus aureus

  https://www.openmicrobiologyjournal.com/VOLUME/14/PAGE/164/FULLTEXT/

  The immune system is responsible for protecting the host from pathogens, and it has evolved to deal with these pathogens. […] Staphylococcus aureus is a significant pathogen of humans that encodes several virulence factors that can modulate or evade from the innate and adaptive arm of the immune system. Overall, the immune reaction toward S. aureus contributes to stimulate innate and adaptive reactions. […] A major consequence is the stimulation of phagocytic immune cells like neutrophils and macrophages. […] The innate immune cells can be induced via Toll-like Receptors that enhance antibacterial reactions, stimulate inflammation, and trigger effector cells. […] TLR-1, TLR-2, and TLR-6 detect the cell wall components S. aureus, particularly peptidoglycan and lipopeptides. […] It is supposed that TLR2 molecules are essential for localized and systemic S. aureus infection.

• #72 The Human Immune System toward Staphylococcus aureus

  https://www.openmicrobiologyjournal.com/VOLUME/14/PAGE/164/FULLTEXT/

  The immune system is responsible for protecting the host from pathogens, and it has evolved to deal with these pathogens. […] Staphylococcus aureus is a significant pathogen of humans that encodes several virulence factors that can modulate or evade from the innate and adaptive arm of the immune system. Overall, the immune reaction toward S. aureus contributes to stimulate innate and adaptive reactions. […] A major consequence is the stimulation of phagocytic immune cells like neutrophils and macrophages. […] The innate immune cells can be induced via Toll-like Receptors that enhance antibacterial reactions, stimulate inflammation, and trigger effector cells. […] TLR-1, TLR-2, and TLR-6 detect the cell wall components S. aureus, particularly peptidoglycan and lipopeptides. […] It is supposed that TLR2 molecules are essential for localized and systemic S. aureus infection.

• #73 The Human Immune System toward Staphylococcus aureus

  https://www.openmicrobiologyjournal.com/VOLUME/14/PAGE/164/FULLTEXT/

  The NOD-1, NOD-2 and intracellular PRRs that recognized microbial peptidoglycan stimulate antimicrobial peptide formation, inflammation, and phagocytic effector activities. […] The NOD2-deficient mouse is very susceptible to systemic and skin infections of S. aureus when compared with wild type counterparts. […] S. aureus cells trigger different antimicrobial effector activities, when coated with opsonins like C3b and IgG. […] Pharmacologic inhibition and genetic deletion of nitric oxide production render mice susceptible to S. aureus infection. […] Neutrophils kill pathogens by degranulation of toxic components. […] Neutrophils liberate structures of DNA named NET (neutrophil extracellular trap), as an additional effector mechanism to control S. aureus infection, that formed in a mechanism dependent on a TLR2 and MyD88 and is necessary for containing S. aureus in the host skin to prevent bacteremia.

• #74 The Human Immune System toward Staphylococcus aureus

  https://www.openmicrobiologyjournal.com/VOLUME/14/PAGE/164/FULLTEXT/

  The immune system is responsible for protecting the host from pathogens, and it has evolved to deal with these pathogens. […] Staphylococcus aureus is a significant pathogen of humans that encodes several virulence factors that can modulate or evade from the innate and adaptive arm of the immune system. Overall, the immune reaction toward S. aureus contributes to stimulate innate and adaptive reactions. […] A major consequence is the stimulation of phagocytic immune cells like neutrophils and macrophages. […] The innate immune cells can be induced via Toll-like Receptors that enhance antibacterial reactions, stimulate inflammation, and trigger effector cells. […] TLR-1, TLR-2, and TLR-6 detect the cell wall components S. aureus, particularly peptidoglycan and lipopeptides. […] It is supposed that TLR2 molecules are essential for localized and systemic S. aureus infection.

• #75 Immune System Evasion Mechanisms in Staphylococcus aureus: Current Understanding – Journal of Pure and Applied Microbiology

  https://microbiologyjournal.org/immune-system-evasion-mechanisms-in-staphylococcus-aureus-current-understanding/

  It has been shown that S. aureus developed different mechanisms to avoid the action of the complement system by producing a number of proteins that can change and affect the stages of the complement cascade, these mechanisms include; preventing complement identification; cleavage of complement proteins; and/or inhibit the interaction of complement receptors on phagocytes. […] S. aureus produces many significant factors to avoid and evade from phagocytosis. It expresses anti-opsonic proteins bound to the surface and a capsule of polysaccharides which: (a) interfere with antibodies and with the formation of complement through classical and alternative pathways, (b) inhibit their interaction to neutrophil complement receptor and Fc receptor. […] S. aureus is a common pathogen that has the ability to secrete and produce toxins which contribute to the damage of host cells membranes. The expression of cytolytic toxins that damage leukocytes contributes to development of abscesses by the killing of neutrophils that are attempting to engulf and kill the bacteria. […] It seems clear that S. aureus is a widespread organism that lives as a normal flora in the nose and on the skin of humans and animals. It is a very successful pathogen because of its ability to express and produce virulence factors to evade the recognition and the killing of the host immune cells.

• #76 The Human Immune System toward Staphylococcus aureus

  https://www.openmicrobiologyjournal.com/VOLUME/14/PAGE/164/FULLTEXT/

  Nevertheless, S. aureus cells can destroy NET, and the degradation product 2-deoxyadenosine that stimulates apoptosis in macrophage cells, which raise bacterial survival in the abscess. […] The significance of antibody-mediated protection toward microbial infectious agents is found by demonstrating this event that the absence of B lymphocyte maturation causes susceptibility against infections with encapsulated bacteria and viruses. […] The notable absence of raised susceptibility in this regard to S. aureus argues that antibody is un-significant in protection toward infection of S. aureus. […] Nevertheless, it has found that early cutaneous S. aureus infection could stimulate antibody-mediated support toward a subsequent microbial infection in certain mouse strains. […] T lymphocyte has a dual function: (1) it is important for the production of opposing antibodies because T cell is essential for maturation of antibody affinity as well as class switches, (2) T cells promote phagocytosis by absorbing neutrophils and macrophages from the bone marrow to the site of infection.

• #77 The Human Immune System toward Staphylococcus aureus

  https://www.openmicrobiologyjournal.com/VOLUME/14/PAGE/164/FULLTEXT/

  Nevertheless, S. aureus cells can destroy NET, and the degradation product 2-deoxyadenosine that stimulates apoptosis in macrophage cells, which raise bacterial survival in the abscess. […] The significance of antibody-mediated protection toward microbial infectious agents is found by demonstrating this event that the absence of B lymphocyte maturation causes susceptibility against infections with encapsulated bacteria and viruses. […] The notable absence of raised susceptibility in this regard to S. aureus argues that antibody is un-significant in protection toward infection of S. aureus. […] Nevertheless, it has found that early cutaneous S. aureus infection could stimulate antibody-mediated support toward a subsequent microbial infection in certain mouse strains. […] T lymphocyte has a dual function: (1) it is important for the production of opposing antibodies because T cell is essential for maturation of antibody affinity as well as class switches, (2) T cells promote phagocytosis by absorbing neutrophils and macrophages from the bone marrow to the site of infection.

• #78 The Human Immune System toward Staphylococcus aureus

  https://www.openmicrobiologyjournal.com/VOLUME/14/PAGE/164/FULLTEXT/

  Nevertheless, S. aureus cells can destroy NET, and the degradation product 2-deoxyadenosine that stimulates apoptosis in macrophage cells, which raise bacterial survival in the abscess. […] The significance of antibody-mediated protection toward microbial infectious agents is found by demonstrating this event that the absence of B lymphocyte maturation causes susceptibility against infections with encapsulated bacteria and viruses. […] The notable absence of raised susceptibility in this regard to S. aureus argues that antibody is un-significant in protection toward infection of S. aureus. […] Nevertheless, it has found that early cutaneous S. aureus infection could stimulate antibody-mediated support toward a subsequent microbial infection in certain mouse strains. […] T lymphocyte has a dual function: (1) it is important for the production of opposing antibodies because T cell is essential for maturation of antibody affinity as well as class switches, (2) T cells promote phagocytosis by absorbing neutrophils and macrophages from the bone marrow to the site of infection.

• #79 Molecular Pathogenesis of Staphylococcus aureus Infection

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2919328/

  Defense against ROS is mediated in S. aureus by deployment of a large number of antioxidant enzymes that neutralize ROS and RNS. […] As a preemptive measure, S. aureus counters by secreting specific toxins, which lyse neutrophils. […] Apart from evasion of host immune defense, bacterial survival within the human host is dependent on successful acquisition of nutrients, particularly iron. […] A severe bacterial infection normally induces the host to mount an adaptive immune response within seven to ten days to limit the ongoing infection and prevent future reinfections. […] However, one of the hallmarks of S. aureus biology is the ability of the pathogen to infect the human host repeatedly throughout life. […] Other virulence mechanisms of clinical significance include biofilm formation which allows S. aureus to persist on plastics and resist host defenses or antibiotics, and small colony variants which help S. aureus survive in a metabolically inactive state under harsh conditions.

• #80 The Rockefeller University » The genetic underpinnings of severe staph infections

  https://www.rockefeller.edu/news/32247-the-genetic-underpinnings-of-severe-staph-infections/

  A common culprit of skin and respiratory infections, Staphylococcus aureus is highly unpredictable. Between 20 and 30 percent of people carry quiet colonies on their skin and in their nostrils, which seldom cause problems beyond the occasional rash. But in some cases these bacteria cause infections that lead to deadly complications, such as pneumonia, deep skin infections, and sepsis. Until recently, there was no way to predict which infections may take a lethal turn. […] Now, a new study describes mutations that predispose patients to severe staph infections. The research, published in Science, identifies a mutated gene common to multiple patients who suffer life-threatening infections and suggests that people living with a genetic condition known as 5p- or Cri-du-chat syndrome may be at similar risk.

• #81 May 19: Genetic condition causes severe Staphylococcus aureus infections – UMC Utrecht

  https://www.umcutrecht.nl/en/over-ons/nieuws/infection-and-immunity/may-19-genetic-condition-causes-severe-staphylococcus-aureus-infections

  International research – coordinated by clinical microbiologist and clinician-scientist Andrs Spaan (UMC Utrecht and The Rockefeller University) – has unraveled why, after infection with the notorious bacterium Staphylococcus aureus, some people fall severely ill. […] In our patients with severe staphylococcal disease, we found an enrichment for rare heterozygous mutations in a gene named OTULIN. […] Patients carrying this genetic defect had an increased risk to suffer from episodes of life-threatening necrosis of the skin or lungs. […] It appeared that the disorder operates by haploinsufficiency. […] We discovered that OTULIN governs a key mechanism of cell-intrinsic anti-staphylococcal immunity in humans. […] Our study reveals the potential of developing therapies that interfere with bacterial toxins to prevent or treat infections like those caused by S. aureus.

• #82 The Rockefeller University » The genetic underpinnings of severe staph infections

  https://www.rockefeller.edu/news/32247-the-genetic-underpinnings-of-severe-staph-infections/

  The genetic mechanism was important to pin down, Spaan says. People with two functional copies of the gene appear to be healthy, those with no functional copies have autoinflammatory disease, and those with one functional copy are susceptible to severe staph infections. […] We were able to demonstrate that this susceptibility is driven by the fact that they had only one functional copy of OTULIN, Spaan says. In many ways, these patients looked genetically similar to the patients we had identified with severe staph infections. […] The findings do not imply that everyone with OTULIN haploinsufficiency or 5p- syndrome will contract severe infections. In fact, the initial results of the study suggested that only 30 percent of individuals with these mutations develop severe disease. […] One potential answer has already surfaced. Spaan and colleagues found that individuals with OTULIN mutations but no sign of severe disease had high levels of antibodies that neutralize the toxin produced by S. aureus, perhaps due to prior exposure to the common skin bacteria. Individuals with severe disease, on the other hand, had precious few antibodies.

• #83 Discovery of a mechanism that allows Staphylococcus aureus to survive in blood | INRAE

  https://www.inrae.fr/en/news/discovery-mechanism-allows-staphylococcus-aureus-survive-blood

  Staphylococcus aureus detects heme, a molecule that is toxic to bacteria, using a specific bio-sensor that then triggers synthesis of a protective barrier on the bacteriums surface. […] This mechanism allows the pathogen to survive and propagate in blood, thereby enabling the infection to spread. […] These researchers discovered that Staphylococcus aureus can detect heme using a specific sensor named HssS, which is found on its membrane. When the sensor detects heme, it triggers a defense mechanism in golden staph, which synthesizes a heme efflux pump that ejects that substance from the bacterium. This creates a protective barrier that allows Staphylococcus aureus to survive in the bloodstream and spread the infection. […] Given the problems with antibiotic resistance, these results open new pathways for antibiotic strategies to control Staphylococcus aureus by identifying molecules that inhibit the HssS sensor, thereby decreasing the bacterium’s virulence.

• #84 Toxin-Induced Necroptosis Is a Major Mechanism of Staphylococcus aureus Lung Damage | PLOS Pathogens

  https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004820

  Staphylococcus aureus USA300 strains cause a highly inflammatory necrotizing pneumonia. The virulence of this strain has been attributed to its expression of multiple toxins that have diverse targets including ADAM10, NLRP3 and CD11b. We demonstrate that induction of necroptosis through RIP1/RIP3/MLKL signaling is a major consequence of S. aureus toxin production. […] Toxin-associated pore formation was essential, as cell death was blocked by exogenous K+ or dextran. […] These findings indicate that toxin-induced necroptosis is a major cause of lung pathology in S. aureus pneumonia and suggest the possibility of targeting components of this signaling pathway as a therapeutic strategy. […] We demonstrate that Hla also targets immune cells by specifically inducing necroptosis as evidenced by its ability to induce MLKL phosphorylation and dose-dependent induction of macrophage death that was prevented by inhibition of MLKL.

• #85 Discovery of a mechanism that allows Staphylococcus aureus to survive in blood | INRAE

  https://www.inrae.fr/en/news/discovery-mechanism-allows-staphylococcus-aureus-survive-blood

  Staphylococcus aureus detects heme, a molecule that is toxic to bacteria, using a specific bio-sensor that then triggers synthesis of a protective barrier on the bacteriums surface. […] This mechanism allows the pathogen to survive and propagate in blood, thereby enabling the infection to spread. […] These researchers discovered that Staphylococcus aureus can detect heme using a specific sensor named HssS, which is found on its membrane. When the sensor detects heme, it triggers a defense mechanism in golden staph, which synthesizes a heme efflux pump that ejects that substance from the bacterium. This creates a protective barrier that allows Staphylococcus aureus to survive in the bloodstream and spread the infection. […] Given the problems with antibiotic resistance, these results open new pathways for antibiotic strategies to control Staphylococcus aureus by identifying molecules that inhibit the HssS sensor, thereby decreasing the bacterium’s virulence.

• #86 May 19: Genetic condition causes severe Staphylococcus aureus infections – UMC Utrecht

  https://www.umcutrecht.nl/en/over-ons/nieuws/infection-and-immunity/may-19-genetic-condition-causes-severe-staphylococcus-aureus-infections

  International research – coordinated by clinical microbiologist and clinician-scientist Andrs Spaan (UMC Utrecht and The Rockefeller University) – has unraveled why, after infection with the notorious bacterium Staphylococcus aureus, some people fall severely ill. […] In our patients with severe staphylococcal disease, we found an enrichment for rare heterozygous mutations in a gene named OTULIN. […] Patients carrying this genetic defect had an increased risk to suffer from episodes of life-threatening necrosis of the skin or lungs. […] It appeared that the disorder operates by haploinsufficiency. […] We discovered that OTULIN governs a key mechanism of cell-intrinsic anti-staphylococcal immunity in humans. […] Our study reveals the potential of developing therapies that interfere with bacterial toxins to prevent or treat infections like those caused by S. aureus.

• #87 The Rockefeller University » The genetic underpinnings of severe staph infections

  https://www.rockefeller.edu/news/32247-the-genetic-underpinnings-of-severe-staph-infections/

  Further investigation into genetic predisposition to diseases, particularly those as difficult to treat as staphylococcal infections, may contribute to the development of future therapeutics. Studies on these disorders can act as a compass, Spaan says, Our research clarifies the interactions between hosts and pathogens, revealing scientific insights into pathogenesis and immunity.

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