Materiały źródłowe

• #1 Pathogenesis, epidemiology and control of Group A Streptococcus infection | Nature Reviews Microbiology

  https://www.nature.com/articles/s41579-023-00865-7

  Streptococcus pyogenes (Group A Streptococcus; GAS) is exquisitely adapted to the human host, resulting in asymptomatic infection, pharyngitis, pyoderma, scarlet fever or invasive diseases, with potential for triggering post-infection immune sequelae. […] GAS deploys a range of virulence determinants to allow colonization, dissemination within the host and transmission, disrupting both innate and adaptive immune responses to infection. […] The recent identification of clinical GAS isolates with reduced penicillin sensitivity and increasing macrolide resistance threatens both frontline and penicillin-adjunctive antibiotic treatment. […] This paper reports demonstrating that SpeB triggers keratinocyte pyroptosis by cleaving GSDMA, providing a mechanism for inflammatory response stimulation at the epithelial cell layer.

• #2 Pathogenesis of Group A Streptococcal Infections

  https://pmc.ncbi.nlm.nih.gov/articles/PMC88944/

  Group A streptococci are model extracellular gram-positive pathogens responsible for pharyngitis, impetigo, rheumatic fever, and acute glomerulonephritis. […] The strong resistance of the group A streptococcus to phagocytosis is related to factor H and fibrinogen binding by M protein and to disarming complement component C5a by the C5a peptidase. […] Molecular mimicry appears to play a role in autoimmune mechanisms involved in rheumatic fever, while nephritis strain-associated proteins may lead to immune-mediated acute glomerulonephritis. […] Several virulence factors of group A streptococci are likely to be involved in the pathogenesis of toxic shock, invasion of soft tissues and skin, and necrotizing fasciitis. […] The pyrogenic exotoxins are potentially responsible for at least some of the manifestations of toxic streptococcal syndrome.

• #3 Group A streptococcus: Virulence factors and pathogenic mechanisms – UpToDate

  https://www.uptodate.com/contents/group-a-streptococcus-virulence-factors-and-pathogenic-mechanisms

  Group A streptococcus: Virulence factors and pathogenic mechanisms […] The pathogenic mechanisms underlying these infections are poorly understood, largely because each is the culmination of highly complex interactions between the human host defense mechanisms and specific virulence factors of the organism. […] A number of different cell-surface molecules and secreted products of GAS have been identified as virulence factors. […] Anti-phagocytic properties […] Mechanisms of fever induction […] Cytokine induction […] Role in innate immunity.

• #4 Pathogenesis of Group A Streptococcal Infections

  https://pmc.ncbi.nlm.nih.gov/articles/PMC88944/

  Group A streptococci are model extracellular gram-positive pathogens responsible for pharyngitis, impetigo, rheumatic fever, and acute glomerulonephritis. […] The strong resistance of the group A streptococcus to phagocytosis is related to factor H and fibrinogen binding by M protein and to disarming complement component C5a by the C5a peptidase. […] Molecular mimicry appears to play a role in autoimmune mechanisms involved in rheumatic fever, while nephritis strain-associated proteins may lead to immune-mediated acute glomerulonephritis. […] Several virulence factors of group A streptococci are likely to be involved in the pathogenesis of toxic shock, invasion of soft tissues and skin, and necrotizing fasciitis. […] The pyrogenic exotoxins are potentially responsible for at least some of the manifestations of toxic streptococcal syndrome.

• #5 Group A Streptococcus – National Collaborating Centre for Infectious Diseases

  https://nccid.ca/debrief/group-a-streptococcus/

  Group A streptococcal disease (GAS) is caused by the bacteria Streptococcus pyogenes (S. pyogenes) gram positive, beta-hemolytic bacteria that can be found on the skin or in the throat. […] Several virulence factors contribute to human infection by GAS via the secretion or release of a variety of extracellular products. The main virulence factors include, but are not limited to, the presence of M protein fragments assisting with GAS colonization, invasions by the toxins streptolysin S and O, bacterial dissemination by streptokinase, and more. […] GAS is responsible for a range of diseases ranging from non-invasive to invasive. The vast majority of GAS diseases are mild and non-invasive, such as strep throat (acute pharyngitis), skin and soft tissue infections (e.g., impetigo and cellulitis), and fevers and rashes (e.g., scarlet fever). In rare cases, S. pyogenes enter parts of the body where bacteria are not normally found, such as in the blood, deep tissue, or lungs. These infections are called invasive GAS (iGAS) and can lead to severe diseases such as necrotizing fasciitis (flesh eating disease), toxic shock syndrome (TSS), and lung infections (e.g., pneumonia).

• #6 Group A Strep | Caparon Lab | Washington University in St. Louis

  https://caparonlab.wustl.edu/group-a-strep/

  Streptococcus pyogenes owes its major success as a pathogen to its ability to colonize and rapidly multiply and spread in its host while evading phagocytosis and confusing the immune system. […] Acute diseases associated with Streptococcus pyogenes occur chiefly in the respiratory tract, bloodstream, or the skin. Streptococcal disease is most often a respiratory infection (pharyngitis or tonsillitis) or a skin infection (pyoderma). […] Two post streptococcal sequelae, rheumatic fever and glomerulonephritis, may follow streptococcal disease, and occur in 1-3% of untreated infections. These conditions and their pathology are not attributable to dissemination of bacteria, but to aberrant immunological reactions to Group A streptococcal antigens. […] The cell surface of Streptococcus pyogenes accounts for many of the bacterium’s determinants of virulence, especially those concerned with colonization and evasion of phagocytosis and the host immune responses.

• #7 Streptococcus pyogenes: Pathogenesis and the Current Status of Vaccines

  https://www.mdpi.com/2076-393X/11/9/1510

  Streptococcus pyogenes (GAS; also known as group A Streptococcus) is a Gram-positive coccus that causes a variety of infectious diseases, including (1) superficial infections (purulent tonsillitis, erysipelas, pharyngitis, and cellulitis), (2) toxin-mediated diseases (scarlet fever and streptococcal toxic shock syndrome (STSS)), (3) immune-mediated diseases (acute rheumatic fever (ARF) and rheumatic heart disease (RHD)), and invasive infections (necrotizing fasciitis, bacteremia, and meningitis) [1,2,3]. […] GAS causes damage to host cells, tissues, and the immune system by secreting a large number of virulence factors. For example, the M protein of GAS binds to fibronectin (Fn) on the surface of the host cell to enter epithelial or endothelial cells, which is considered key to the evolutionary success and adaptability of GAS [6]. After colonization, GAS must evade the host’s innate immune system to invade deeper tissue sites and trigger severe infections. Autophagy is one such innate immune defense mechanism against intracellular GAS; however, streptococcal cysteine protease (SpeB) can degrade autophagy adaptor proteins p62, NDP52, and NBR1 to evade the clearance mechanism of the autophagy pathway [7].

• #8 Group A Strep | Caparon Lab | Washington University in St. Louis

  https://caparonlab.wustl.edu/group-a-strep/

  Streptococcus pyogenes owes its major success as a pathogen to its ability to colonize and rapidly multiply and spread in its host while evading phagocytosis and confusing the immune system. […] Acute diseases associated with Streptococcus pyogenes occur chiefly in the respiratory tract, bloodstream, or the skin. Streptococcal disease is most often a respiratory infection (pharyngitis or tonsillitis) or a skin infection (pyoderma). […] Two post streptococcal sequelae, rheumatic fever and glomerulonephritis, may follow streptococcal disease, and occur in 1-3% of untreated infections. These conditions and their pathology are not attributable to dissemination of bacteria, but to aberrant immunological reactions to Group A streptococcal antigens. […] The cell surface of Streptococcus pyogenes accounts for many of the bacterium’s determinants of virulence, especially those concerned with colonization and evasion of phagocytosis and the host immune responses.

• #9 Group A Strep | Caparon Lab | Washington University in St. Louis

  https://caparonlab.wustl.edu/group-a-strep/

  Streptococcus pyogenes owes its major success as a pathogen to its ability to colonize and rapidly multiply and spread in its host while evading phagocytosis and confusing the immune system. […] Acute diseases associated with Streptococcus pyogenes occur chiefly in the respiratory tract, bloodstream, or the skin. Streptococcal disease is most often a respiratory infection (pharyngitis or tonsillitis) or a skin infection (pyoderma). […] Two post streptococcal sequelae, rheumatic fever and glomerulonephritis, may follow streptococcal disease, and occur in 1-3% of untreated infections. These conditions and their pathology are not attributable to dissemination of bacteria, but to aberrant immunological reactions to Group A streptococcal antigens. […] The cell surface of Streptococcus pyogenes accounts for many of the bacterium’s determinants of virulence, especially those concerned with colonization and evasion of phagocytosis and the host immune responses.

• #10 Pathogenesis, epidemiology and control of Group A Streptococcus infection | Nature Reviews Microbiology

  https://www.nature.com/articles/s41579-023-00865-7

  Streptococcus pyogenes (Group A Streptococcus; GAS) is exquisitely adapted to the human host, resulting in asymptomatic infection, pharyngitis, pyoderma, scarlet fever or invasive diseases, with potential for triggering post-infection immune sequelae. […] GAS deploys a range of virulence determinants to allow colonization, dissemination within the host and transmission, disrupting both innate and adaptive immune responses to infection. […] The recent identification of clinical GAS isolates with reduced penicillin sensitivity and increasing macrolide resistance threatens both frontline and penicillin-adjunctive antibiotic treatment. […] This paper reports demonstrating that SpeB triggers keratinocyte pyroptosis by cleaving GSDMA, providing a mechanism for inflammatory response stimulation at the epithelial cell layer.

• #11 Pathogenesis of Group A Streptococcal Infections – Anna Henningham – Discovery Medicine

  https://www.discoverymedicine.com/Anna-Henningham/2012/05/16/pathogenesis-of-group-a-streptococcal-infections/

  Group A Streptococcus (GAS; Streptococcus pyogenes) is a Gram-positive human pathogen which typically colonizes the throat or skin of the host. […] GAS diseases are underpinned by an extensive repertoire of virulence determinants that are differentially regulated in direct response to a battery of environmental signals within the host. […] The trigger for rapidly progressive invasive GAS disease has also been linked to the capacity of GAS to hijack host molecules for redeployment as virulence factors. […] It is thought there are three stages in the pathogenesis of GAS pharyngitis: i) adherence to the host pharyngeal epithelial tissue, often followed by invasion into and persistence in host epithelial cells, ii) nutrient acquisition to enable proliferation in the host, and iii) evasion of the host immune response.

• #12 Group A streptococcus: Virulence factors and pathogenic mechanisms – UpToDate

  https://www.uptodate.com/contents/group-a-streptococcus-virulence-factors-and-pathogenic-mechanisms

  Group A streptococcus: Virulence factors and pathogenic mechanisms […] The pathogenic mechanisms underlying these infections are poorly understood, largely because each is the culmination of highly complex interactions between the human host defense mechanisms and specific virulence factors of the organism. […] A number of different cell-surface molecules and secreted products of GAS have been identified as virulence factors. […] Anti-phagocytic properties […] Mechanisms of fever induction […] Cytokine induction […] Role in innate immunity.

• #13 Pathogenesis of Group A Streptococcal Infections

  https://pmc.ncbi.nlm.nih.gov/articles/PMC88944/

  The antiphagocytic behavior of group A streptococci is also mediated by the binding of fibrinogen to the surface of M protein. […] The C5a peptidase cleaves the complement-derived chemotaxin C5a at its PMN-binding site. […] The C5a peptidase is a proteolytic enzyme (endopeptidase) found on the surface of group A streptococci. […] The C5a peptidase is encoded by a gene which is regulated by mga in concert with M protein. […] The M protein is a major surface protein and virulence factor of group A streptococci, with more than 80 distinct serotypes identified. […] The M protein extends from the cell surface as an alpha-helical coiled-coil dimer which appears as fibrils on the surface of group A streptococci. […] The M protein inhibits phagocytosis, which is a primary virulence mechanism for survival in tissues.

• #14 Pathogenesis of Group A Streptococcal Infections

  https://pmc.ncbi.nlm.nih.gov/articles/PMC88944/

  The antiphagocytic behavior of group A streptococci is also mediated by the binding of fibrinogen to the surface of M protein. […] The C5a peptidase cleaves the complement-derived chemotaxin C5a at its PMN-binding site. […] The C5a peptidase is a proteolytic enzyme (endopeptidase) found on the surface of group A streptococci. […] The C5a peptidase is encoded by a gene which is regulated by mga in concert with M protein. […] The M protein is a major surface protein and virulence factor of group A streptococci, with more than 80 distinct serotypes identified. […] The M protein extends from the cell surface as an alpha-helical coiled-coil dimer which appears as fibrils on the surface of group A streptococci. […] The M protein inhibits phagocytosis, which is a primary virulence mechanism for survival in tissues.

• #15 Pathogenesis of Group A Streptococcal Infections

  https://pmc.ncbi.nlm.nih.gov/articles/PMC88944/

  The antiphagocytic behavior of group A streptococci is also mediated by the binding of fibrinogen to the surface of M protein. […] The C5a peptidase cleaves the complement-derived chemotaxin C5a at its PMN-binding site. […] The C5a peptidase is a proteolytic enzyme (endopeptidase) found on the surface of group A streptococci. […] The C5a peptidase is encoded by a gene which is regulated by mga in concert with M protein. […] The M protein is a major surface protein and virulence factor of group A streptococci, with more than 80 distinct serotypes identified. […] The M protein extends from the cell surface as an alpha-helical coiled-coil dimer which appears as fibrils on the surface of group A streptococci. […] The M protein inhibits phagocytosis, which is a primary virulence mechanism for survival in tissues.

• #16 Streptococcus pyogenes: Pathogenesis and the Current Status of Vaccines

  https://www.mdpi.com/2076-393X/11/9/1510

  The genome sequences of GAS encode multiple virulence factors, which are crucial for tissue cell colonization and invasive disease progression [2,13]. Understanding the various virulence mechanisms of GAS will help us better understand the causes of disease progression and improve vaccine design and development. […] The M protein is an α-helical dimer located on the GAS surface. The basic structural components of the M protein consist of an N-terminal hypervariable region, central domain, and C-terminal conserved region [14]. Due to the high variability of the N terminus of the M protein, it exhibits quite complex antigenic diversity. M proteins bind to extracellular matrix (ECM) components such as fibronectin (Fn) to promote GAS colonization. In addition, GAS is internalized into epithelial cells by cell surface integrin α5β1 or CD46, which evades the surveillance of the immune system [15].

• #17 Streptococcus pyogenes: Pathogenesis and the Current Status of Vaccines

  https://www.mdpi.com/2076-393X/11/9/1510

  The genome sequences of GAS encode multiple virulence factors, which are crucial for tissue cell colonization and invasive disease progression [2,13]. Understanding the various virulence mechanisms of GAS will help us better understand the causes of disease progression and improve vaccine design and development. […] The M protein is an α-helical dimer located on the GAS surface. The basic structural components of the M protein consist of an N-terminal hypervariable region, central domain, and C-terminal conserved region [14]. Due to the high variability of the N terminus of the M protein, it exhibits quite complex antigenic diversity. M proteins bind to extracellular matrix (ECM) components such as fibronectin (Fn) to promote GAS colonization. In addition, GAS is internalized into epithelial cells by cell surface integrin α5β1 or CD46, which evades the surveillance of the immune system [15].

• #18 Streptococcus pyogenes: Pathogenesis and the Current Status of Vaccines

  https://www.mdpi.com/2076-393X/11/9/1510

  The genome sequences of GAS encode multiple virulence factors, which are crucial for tissue cell colonization and invasive disease progression [2,13]. Understanding the various virulence mechanisms of GAS will help us better understand the causes of disease progression and improve vaccine design and development. […] The M protein is an α-helical dimer located on the GAS surface. The basic structural components of the M protein consist of an N-terminal hypervariable region, central domain, and C-terminal conserved region [14]. Due to the high variability of the N terminus of the M protein, it exhibits quite complex antigenic diversity. M proteins bind to extracellular matrix (ECM) components such as fibronectin (Fn) to promote GAS colonization. In addition, GAS is internalized into epithelial cells by cell surface integrin α5β1 or CD46, which evades the surveillance of the immune system [15].

• #19 Pathogenesis of Group A Streptococcal Infections

  https://pmc.ncbi.nlm.nih.gov/articles/PMC88944/

  The antiphagocytic behavior of group A streptococci is also mediated by the binding of fibrinogen to the surface of M protein. […] The C5a peptidase cleaves the complement-derived chemotaxin C5a at its PMN-binding site. […] The C5a peptidase is a proteolytic enzyme (endopeptidase) found on the surface of group A streptococci. […] The C5a peptidase is encoded by a gene which is regulated by mga in concert with M protein. […] The M protein is a major surface protein and virulence factor of group A streptococci, with more than 80 distinct serotypes identified. […] The M protein extends from the cell surface as an alpha-helical coiled-coil dimer which appears as fibrils on the surface of group A streptococci. […] The M protein inhibits phagocytosis, which is a primary virulence mechanism for survival in tissues.

• #20 Streptococcus pyogenes – Wikipedia

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

  S. pyogeneshas several virulence factors that enable it to attach to host tissues, evade the immune response, and spread by penetrating host tissue layers. […] A carbohydrate-based bacterial capsule composed of hyaluronic acid surrounds the bacterium, protecting it from phagocytosis by neutrophils. […] In addition, the capsule and several factors embedded in the cell wall, including M protein, lipoteichoic acid, and protein F (SfbI) facilitate attachment to various host cells. […] M protein also inhibits opsonization by the alternative complement pathway by binding to host complement regulators. […] The M protein found on some serotypes is also able to prevent opsonization by binding to fibrinogen. […] However, the M protein is also the weakest point in this pathogen’s defense, as antibodies produced by the immune system against M protein target the bacteria for engulfment by phagocytes.

• #21 Streptococcus pyogenes – Wikipedia

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

  S. pyogeneshas several virulence factors that enable it to attach to host tissues, evade the immune response, and spread by penetrating host tissue layers. […] A carbohydrate-based bacterial capsule composed of hyaluronic acid surrounds the bacterium, protecting it from phagocytosis by neutrophils. […] In addition, the capsule and several factors embedded in the cell wall, including M protein, lipoteichoic acid, and protein F (SfbI) facilitate attachment to various host cells. […] M protein also inhibits opsonization by the alternative complement pathway by binding to host complement regulators. […] The M protein found on some serotypes is also able to prevent opsonization by binding to fibrinogen. […] However, the M protein is also the weakest point in this pathogen’s defense, as antibodies produced by the immune system against M protein target the bacteria for engulfment by phagocytes.

• #22 Streptococcus pyogenes – Wikipedia

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

  S. pyogeneshas several virulence factors that enable it to attach to host tissues, evade the immune response, and spread by penetrating host tissue layers. […] A carbohydrate-based bacterial capsule composed of hyaluronic acid surrounds the bacterium, protecting it from phagocytosis by neutrophils. […] In addition, the capsule and several factors embedded in the cell wall, including M protein, lipoteichoic acid, and protein F (SfbI) facilitate attachment to various host cells. […] M protein also inhibits opsonization by the alternative complement pathway by binding to host complement regulators. […] The M protein found on some serotypes is also able to prevent opsonization by binding to fibrinogen. […] However, the M protein is also the weakest point in this pathogen’s defense, as antibodies produced by the immune system against M protein target the bacteria for engulfment by phagocytes.

• #23 Group A Strep | Caparon Lab | Washington University in St. Louis

  https://caparonlab.wustl.edu/group-a-strep/

  The M proteins are clearly virulence factors associated with both colonization and resistance to phagocytosis. […] The capsule of S. pyogenes is non-antigenic since it is composed of hyaluronic acid, which is chemically similar to that of host connective tissue. […] Colonization of tissues by S. pyogenes is thought to result from a failure in the constitutive defenses (normal flora and other nonspecific defense mechanisms) which allows establishment of the bacterium at a portal of entry (often the upper respiratory tract or the skin) where the organism multiplies and causes an inflammatory purulent lesion. […] The streptococcal invasins act in a variety of ways summarized in Table 1 at the end of this article. Streptococcal invasins lyse eukaryotic cells, including red blood cells and phagocytes; they lyse other host macromolecules, including enzymes and informational molecules; they allow the bacteria to spread among tissues by dissolving host fibrin and intercellular ground substances.

• #24 Immunomodulating Enzymes from Streptococcus pyogenes—In Pathogenesis, as Biotechnological Tools, and as Biological Drugs

  https://www.mdpi.com/2076-2607/12/1/200

  Streptococcus pyogenes, or Group A Streptococcus, is an exclusively human pathogen that causes a wide variety of diseases ranging from mild throat and skin infections to severe invasive disease. The pathogenesis of S. pyogenes infection has been extensively studied, but the pathophysiology, especially of the more severe infections, is still somewhat elusive. One key feature of S. pyogenes is the expression of secreted, surface-associated, and intracellular enzymes that directly or indirectly affect both the innate and adaptive host immune systems. Undoubtedly, S. pyogenes is one of the major bacterial sources for immunomodulating enzymes. Major targets for these enzymes are immunoglobulins that are destroyed or modified through proteolysis or glycan hydrolysis. Furthermore, several enzymes degrade components of the complement system and a group of DNAses degrade host DNA in neutrophil extracellular traps. Additional types of enzymes interfere with cellular inflammatory and innate immunity responses. In this review, we attempt to give a broad overview of the functions of these enzymes and their roles in pathogenesis.

• #25 Pathogenesis of Group A Streptococcal Infections

  https://pmc.ncbi.nlm.nih.gov/articles/PMC88944/

  The antiphagocytic behavior of group A streptococci is also mediated by the binding of fibrinogen to the surface of M protein. […] The C5a peptidase cleaves the complement-derived chemotaxin C5a at its PMN-binding site. […] The C5a peptidase is a proteolytic enzyme (endopeptidase) found on the surface of group A streptococci. […] The C5a peptidase is encoded by a gene which is regulated by mga in concert with M protein. […] The M protein is a major surface protein and virulence factor of group A streptococci, with more than 80 distinct serotypes identified. […] The M protein extends from the cell surface as an alpha-helical coiled-coil dimer which appears as fibrils on the surface of group A streptococci. […] The M protein inhibits phagocytosis, which is a primary virulence mechanism for survival in tissues.

• #26 Pathogenesis of Group A Streptococcal Infections

  https://pmc.ncbi.nlm.nih.gov/articles/PMC88944/

  The antiphagocytic behavior of group A streptococci is also mediated by the binding of fibrinogen to the surface of M protein. […] The C5a peptidase cleaves the complement-derived chemotaxin C5a at its PMN-binding site. […] The C5a peptidase is a proteolytic enzyme (endopeptidase) found on the surface of group A streptococci. […] The C5a peptidase is encoded by a gene which is regulated by mga in concert with M protein. […] The M protein is a major surface protein and virulence factor of group A streptococci, with more than 80 distinct serotypes identified. […] The M protein extends from the cell surface as an alpha-helical coiled-coil dimer which appears as fibrils on the surface of group A streptococci. […] The M protein inhibits phagocytosis, which is a primary virulence mechanism for survival in tissues.

• #27 Pathogenesis of Group A Streptococcal Infections

  https://pmc.ncbi.nlm.nih.gov/articles/PMC88944/

  The antiphagocytic behavior of group A streptococci is also mediated by the binding of fibrinogen to the surface of M protein. […] The C5a peptidase cleaves the complement-derived chemotaxin C5a at its PMN-binding site. […] The C5a peptidase is a proteolytic enzyme (endopeptidase) found on the surface of group A streptococci. […] The C5a peptidase is encoded by a gene which is regulated by mga in concert with M protein. […] The M protein is a major surface protein and virulence factor of group A streptococci, with more than 80 distinct serotypes identified. […] The M protein extends from the cell surface as an alpha-helical coiled-coil dimer which appears as fibrils on the surface of group A streptococci. […] The M protein inhibits phagocytosis, which is a primary virulence mechanism for survival in tissues.

• #28 Streptococcus pyogenes: Pathogenesis and the Current Status of Vaccines

  https://www.mdpi.com/2076-393X/11/9/1510

  SpeB has many substrates and can cleave various host and bacterial proteins. For example, SpeB can degrade immunoglobulins IgA, IgM, IgD, IgE, and IgG into small fragments, reducing antibody-mediated regulatory phagocytosis [19]. SpeB can also degrade C3b, a potent opsonin that recruits phagocytes to infected lesions, thereby inhibiting the migration of phagocytes [20]. […] SCPA is a serine proteinase with the primary function of inactivating the complement pathway by cleaving C3a and C5a proteins [23]. This effectively impairs the infiltration and activation of neutrophils, which is a key defense mechanism of innate immunity. […] Most clinically isolated GAS strains can secrete cytolytic toxins, including SLO and streptolysin S (SLS), whose main function is to cause cell damage by forming pores on the cell membrane. SLO disrupts the host defense mechanisms of macrophages and epithelial cells via Golgi cleavage, promoting GAS intracellular survival and cytotoxicity [26].

• #29 Streptococcus pyogenes: Pathogenesis and the Current Status of Vaccines

  https://www.mdpi.com/2076-393X/11/9/1510

  SpeB has many substrates and can cleave various host and bacterial proteins. For example, SpeB can degrade immunoglobulins IgA, IgM, IgD, IgE, and IgG into small fragments, reducing antibody-mediated regulatory phagocytosis [19]. SpeB can also degrade C3b, a potent opsonin that recruits phagocytes to infected lesions, thereby inhibiting the migration of phagocytes [20]. […] SCPA is a serine proteinase with the primary function of inactivating the complement pathway by cleaving C3a and C5a proteins [23]. This effectively impairs the infiltration and activation of neutrophils, which is a key defense mechanism of innate immunity. […] Most clinically isolated GAS strains can secrete cytolytic toxins, including SLO and streptolysin S (SLS), whose main function is to cause cell damage by forming pores on the cell membrane. SLO disrupts the host defense mechanisms of macrophages and epithelial cells via Golgi cleavage, promoting GAS intracellular survival and cytotoxicity [26].

• #30 Streptococcus pyogenes: Pathogenesis and the Current Status of Vaccines

  https://www.mdpi.com/2076-393X/11/9/1510

  SpeB has many substrates and can cleave various host and bacterial proteins. For example, SpeB can degrade immunoglobulins IgA, IgM, IgD, IgE, and IgG into small fragments, reducing antibody-mediated regulatory phagocytosis [19]. SpeB can also degrade C3b, a potent opsonin that recruits phagocytes to infected lesions, thereby inhibiting the migration of phagocytes [20]. […] SCPA is a serine proteinase with the primary function of inactivating the complement pathway by cleaving C3a and C5a proteins [23]. This effectively impairs the infiltration and activation of neutrophils, which is a key defense mechanism of innate immunity. […] Most clinically isolated GAS strains can secrete cytolytic toxins, including SLO and streptolysin S (SLS), whose main function is to cause cell damage by forming pores on the cell membrane. SLO disrupts the host defense mechanisms of macrophages and epithelial cells via Golgi cleavage, promoting GAS intracellular survival and cytotoxicity [26].

• #31 Streptococcus pyogenes: Pathogenesis and the Current Status of Vaccines

  https://www.mdpi.com/2076-393X/11/9/1510

  SpeB has many substrates and can cleave various host and bacterial proteins. For example, SpeB can degrade immunoglobulins IgA, IgM, IgD, IgE, and IgG into small fragments, reducing antibody-mediated regulatory phagocytosis [19]. SpeB can also degrade C3b, a potent opsonin that recruits phagocytes to infected lesions, thereby inhibiting the migration of phagocytes [20]. […] SCPA is a serine proteinase with the primary function of inactivating the complement pathway by cleaving C3a and C5a proteins [23]. This effectively impairs the infiltration and activation of neutrophils, which is a key defense mechanism of innate immunity. […] Most clinically isolated GAS strains can secrete cytolytic toxins, including SLO and streptolysin S (SLS), whose main function is to cause cell damage by forming pores on the cell membrane. SLO disrupts the host defense mechanisms of macrophages and epithelial cells via Golgi cleavage, promoting GAS intracellular survival and cytotoxicity [26].

• #32 Pathogenesis, epidemiology and control of Group A Streptococcus infection – PubMed

  https://pubmed.ncbi.nlm.nih.gov/36894668/

  The coordinated activities of SLO and NADase further prevent maturation of phagolysosomes, inhibit IL-8 secretion and promote GAS survival in macrophages, where streptolysins SLO and SLS and M protein activate the inflammasome pathway to induce IL-1 production and pyroptosis. SpeB additionally amplifies inflammatory signalling by cleaving and activating pro-IL-1 in an inflammasome-independent manner. […] Survival strategies employed by GAS to escape adaptive immunity include the secretion of the IgG-degrading enzymes IdeS, Mac-2 and EndoS, which enables bacterial escape from IgG opsonization and recognition by FcR on phagocytes. […] Superantigens, by contrast, cause excessive activation of the adaptive immune system by cross-linking MHC class II molecules on antigen-presenting cells (APCs) and T cell receptors (TCRs) in a nonspecific fashion leading to an event known as a cytokine storm.

• #33 Streptococcus pyogenes: Pathogenesis and the Current Status of Vaccines

  https://www.mdpi.com/2076-393X/11/9/1510

  SpeB has many substrates and can cleave various host and bacterial proteins. For example, SpeB can degrade immunoglobulins IgA, IgM, IgD, IgE, and IgG into small fragments, reducing antibody-mediated regulatory phagocytosis [19]. SpeB can also degrade C3b, a potent opsonin that recruits phagocytes to infected lesions, thereby inhibiting the migration of phagocytes [20]. […] SCPA is a serine proteinase with the primary function of inactivating the complement pathway by cleaving C3a and C5a proteins [23]. This effectively impairs the infiltration and activation of neutrophils, which is a key defense mechanism of innate immunity. […] Most clinically isolated GAS strains can secrete cytolytic toxins, including SLO and streptolysin S (SLS), whose main function is to cause cell damage by forming pores on the cell membrane. SLO disrupts the host defense mechanisms of macrophages and epithelial cells via Golgi cleavage, promoting GAS intracellular survival and cytotoxicity [26].

• #34 Streptococcus pyogenes: Pathogenesis and the Current Status of Vaccines

  https://www.mdpi.com/2076-393X/11/9/1510

  SpeB has many substrates and can cleave various host and bacterial proteins. For example, SpeB can degrade immunoglobulins IgA, IgM, IgD, IgE, and IgG into small fragments, reducing antibody-mediated regulatory phagocytosis [19]. SpeB can also degrade C3b, a potent opsonin that recruits phagocytes to infected lesions, thereby inhibiting the migration of phagocytes [20]. […] SCPA is a serine proteinase with the primary function of inactivating the complement pathway by cleaving C3a and C5a proteins [23]. This effectively impairs the infiltration and activation of neutrophils, which is a key defense mechanism of innate immunity. […] Most clinically isolated GAS strains can secrete cytolytic toxins, including SLO and streptolysin S (SLS), whose main function is to cause cell damage by forming pores on the cell membrane. SLO disrupts the host defense mechanisms of macrophages and epithelial cells via Golgi cleavage, promoting GAS intracellular survival and cytotoxicity [26].

• #35 Streptococcus pyogenes: Pathogenesis and the Current Status of Vaccines

  https://www.mdpi.com/2076-393X/11/9/1510

  SpeB has many substrates and can cleave various host and bacterial proteins. For example, SpeB can degrade immunoglobulins IgA, IgM, IgD, IgE, and IgG into small fragments, reducing antibody-mediated regulatory phagocytosis [19]. SpeB can also degrade C3b, a potent opsonin that recruits phagocytes to infected lesions, thereby inhibiting the migration of phagocytes [20]. […] SCPA is a serine proteinase with the primary function of inactivating the complement pathway by cleaving C3a and C5a proteins [23]. This effectively impairs the infiltration and activation of neutrophils, which is a key defense mechanism of innate immunity. […] Most clinically isolated GAS strains can secrete cytolytic toxins, including SLO and streptolysin S (SLS), whose main function is to cause cell damage by forming pores on the cell membrane. SLO disrupts the host defense mechanisms of macrophages and epithelial cells via Golgi cleavage, promoting GAS intracellular survival and cytotoxicity [26].

• #36 Immunomodulating Enzymes from Streptococcus pyogenes—In Pathogenesis, as Biotechnological Tools, and as Biological Drugs

  https://www.mdpi.com/2076-2607/12/1/200

  One key feature of being a successful pathogen is the ability to evade or modulate host immunity against the bacterium itself. S. pyogenes expresses a multitude of secreted, surface-associated, and intracellular molecules that directly or indirectly affect the immune system. A distinct subgroup of immune evasion factors are enzymes that directly target parts of innate and adaptive immunity. […] The cysteine proteinase SpeB has been found to act on key components in both the classical and alternative pathways of complement activation. C3b, an effective opsonin that attracts phagocytic cells to infection sites, has been notably absent around soft tissue infections caused by S. pyogenes. It has also been observed that C3b levels are reduced in the blood serum of patients with streptococcal toxic shock syndrome (STSS), and that SpeB is capable of breaking down C3b in vitro. It has further been demonstrated that SpeB degradation of C3b hampers both opsonization and the subsequent phagocytic destruction of bacteria.

• #37 Pathogenesis, epidemiology and control of Group A Streptococcus infection – PubMed

  https://pubmed.ncbi.nlm.nih.gov/36894668/

  The coordinated activities of SLO and NADase further prevent maturation of phagolysosomes, inhibit IL-8 secretion and promote GAS survival in macrophages, where streptolysins SLO and SLS and M protein activate the inflammasome pathway to induce IL-1 production and pyroptosis. SpeB additionally amplifies inflammatory signalling by cleaving and activating pro-IL-1 in an inflammasome-independent manner. […] Survival strategies employed by GAS to escape adaptive immunity include the secretion of the IgG-degrading enzymes IdeS, Mac-2 and EndoS, which enables bacterial escape from IgG opsonization and recognition by FcR on phagocytes. […] Superantigens, by contrast, cause excessive activation of the adaptive immune system by cross-linking MHC class II molecules on antigen-presenting cells (APCs) and T cell receptors (TCRs) in a nonspecific fashion leading to an event known as a cytokine storm.

• #38 Pathogenesis, epidemiology and control of Group A Streptococcus infection | Nature Reviews Microbiology

  https://www.nature.com/articles/s41579-023-00865-7

  Streptococcus pyogenes (Group A Streptococcus; GAS) is exquisitely adapted to the human host, resulting in asymptomatic infection, pharyngitis, pyoderma, scarlet fever or invasive diseases, with potential for triggering post-infection immune sequelae. […] GAS deploys a range of virulence determinants to allow colonization, dissemination within the host and transmission, disrupting both innate and adaptive immune responses to infection. […] The recent identification of clinical GAS isolates with reduced penicillin sensitivity and increasing macrolide resistance threatens both frontline and penicillin-adjunctive antibiotic treatment. […] This paper reports demonstrating that SpeB triggers keratinocyte pyroptosis by cleaving GSDMA, providing a mechanism for inflammatory response stimulation at the epithelial cell layer.

• #39 Streptococcus pyogenes: Pathogenesis and the Current Status of Vaccines

  https://www.mdpi.com/2076-393X/11/9/1510

  SpyCEP is a conserved and surface-exposed GAS serine protease whose activity is associated with the severity of invasive diseases in humans [28]. In the upper respiratory tract, SpyCEP contributes to the survival of GAS in the nasopharynx but is not necessary [29]. In contrast, the transmission of GAS from the nasopharynx to the lungs is dependent on SpyCEP.

• #40 Streptococcus pyogenes: Pathogenesis and the Current Status of Vaccines

  https://www.mdpi.com/2076-393X/11/9/1510

  SpyCEP is a conserved and surface-exposed GAS serine protease whose activity is associated with the severity of invasive diseases in humans [28]. In the upper respiratory tract, SpyCEP contributes to the survival of GAS in the nasopharynx but is not necessary [29]. In contrast, the transmission of GAS from the nasopharynx to the lungs is dependent on SpyCEP.

• #41 Streptococcus pyogenes: Pathogenesis and the Current Status of Vaccines

  https://www.mdpi.com/2076-393X/11/9/1510

  SpyCEP is a conserved and surface-exposed GAS serine protease whose activity is associated with the severity of invasive diseases in humans [28]. In the upper respiratory tract, SpyCEP contributes to the survival of GAS in the nasopharynx but is not necessary [29]. In contrast, the transmission of GAS from the nasopharynx to the lungs is dependent on SpyCEP.

• #42 Group A Strep | Caparon Lab | Washington University in St. Louis

  https://caparonlab.wustl.edu/group-a-strep/

  Three streptococcal pyrogenic exotoxins (SPE), formerly known as Erythrogenic toxin, are recognized: types A, B, C. These toxins act as superantigens by a mechanism similar to those described for staphylococci. […] The destructive nature of wound infections prompted the popular press to refer to S. pyogenes as flesh-eating bacteria and ski-eating streptococci. The increase in invasive streptococcal disease was associated with emergence of a highly virulent serotype M1 which is disseminated worldwide.

• #43 Group A Strep | Caparon Lab | Washington University in St. Louis

  https://caparonlab.wustl.edu/group-a-strep/

  Three streptococcal pyrogenic exotoxins (SPE), formerly known as Erythrogenic toxin, are recognized: types A, B, C. These toxins act as superantigens by a mechanism similar to those described for staphylococci. […] The destructive nature of wound infections prompted the popular press to refer to S. pyogenes as flesh-eating bacteria and ski-eating streptococci. The increase in invasive streptococcal disease was associated with emergence of a highly virulent serotype M1 which is disseminated worldwide.

• #44 Pathogenesis, epidemiology and control of Group A Streptococcus infection – PubMed

  https://pubmed.ncbi.nlm.nih.gov/36894668/

  The coordinated activities of SLO and NADase further prevent maturation of phagolysosomes, inhibit IL-8 secretion and promote GAS survival in macrophages, where streptolysins SLO and SLS and M protein activate the inflammasome pathway to induce IL-1 production and pyroptosis. SpeB additionally amplifies inflammatory signalling by cleaving and activating pro-IL-1 in an inflammasome-independent manner. […] Survival strategies employed by GAS to escape adaptive immunity include the secretion of the IgG-degrading enzymes IdeS, Mac-2 and EndoS, which enables bacterial escape from IgG opsonization and recognition by FcR on phagocytes. […] Superantigens, by contrast, cause excessive activation of the adaptive immune system by cross-linking MHC class II molecules on antigen-presenting cells (APCs) and T cell receptors (TCRs) in a nonspecific fashion leading to an event known as a cytokine storm.

• #45 Streptococcal toxic shock syndrome in the intensive care unit | Annals of Intensive Care | Full Text

  https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-018-0438-y

  The main characteristic of superantigens is their ability to bind to major histocompatibility (MHC) class II molecules outside of the antigen groove, and the V region of the T cell receptor, cross-linking those two receptors. This triggers the activation of both the antigen-presenting cell and the T lymphocyte, bypassing conventional mechanisms of MHC-limited antigen cell activation. […] Aside from superantigens, S. pyogenes produces and secretes a wide variety of exotoxins and enzymes such as streptolysins, streptokinase, hyaluronidase, and DNAse such as streptodornase and chemokine proteases and toxic molecules that play undoubtedly an important pathogenic role in necrotizing fasciitis and STSS. […] Preexisting skin lesions are the most frequently identified risk factor for invasive GAS infection. Alcohol abuse, chronic lung disease, immunosuppression, intravenous drug use, heart disease, diabetes, cancer, varicella zoster virus infection, and recent child birth have also been identified as risk factors.

• #46 Pathogenesis, epidemiology and control of Group A Streptococcus infection – PubMed

  https://pubmed.ncbi.nlm.nih.gov/36894668/

  The coordinated activities of SLO and NADase further prevent maturation of phagolysosomes, inhibit IL-8 secretion and promote GAS survival in macrophages, where streptolysins SLO and SLS and M protein activate the inflammasome pathway to induce IL-1 production and pyroptosis. SpeB additionally amplifies inflammatory signalling by cleaving and activating pro-IL-1 in an inflammasome-independent manner. […] Survival strategies employed by GAS to escape adaptive immunity include the secretion of the IgG-degrading enzymes IdeS, Mac-2 and EndoS, which enables bacterial escape from IgG opsonization and recognition by FcR on phagocytes. […] Superantigens, by contrast, cause excessive activation of the adaptive immune system by cross-linking MHC class II molecules on antigen-presenting cells (APCs) and T cell receptors (TCRs) in a nonspecific fashion leading to an event known as a cytokine storm.

• #47 Pathogenesis, epidemiology and control of Group A Streptococcus infection – PubMed

  https://pubmed.ncbi.nlm.nih.gov/36894668/

  The coordinated activities of SLO and NADase further prevent maturation of phagolysosomes, inhibit IL-8 secretion and promote GAS survival in macrophages, where streptolysins SLO and SLS and M protein activate the inflammasome pathway to induce IL-1 production and pyroptosis. SpeB additionally amplifies inflammatory signalling by cleaving and activating pro-IL-1 in an inflammasome-independent manner. […] Survival strategies employed by GAS to escape adaptive immunity include the secretion of the IgG-degrading enzymes IdeS, Mac-2 and EndoS, which enables bacterial escape from IgG opsonization and recognition by FcR on phagocytes. […] Superantigens, by contrast, cause excessive activation of the adaptive immune system by cross-linking MHC class II molecules on antigen-presenting cells (APCs) and T cell receptors (TCRs) in a nonspecific fashion leading to an event known as a cytokine storm.

• #48 Pathogenesis of Group A Streptococcal Infections – Anna Henningham – Discovery Medicine

  https://www.discoverymedicine.com/Anna-Henningham/2012/05/16/pathogenesis-of-group-a-streptococcal-infections/

  Several adhesins and GAS molecules have been implicated in GAS adhesion to and invasion of host epithelial cells (both cutaneous and mucosal) including C5a peptidase, FbaA, FBP54, hyaluronic acid capsule, Lbp, Lsp, LTA, M protein, pili, Protein F1, Protein F2, SEN, SlaA, and SOF. […] Intracellular persistence of GAS has been linked to recurrent cases of pharyngitis and may potentially contribute to the failure of penicillin during treatment. […] In addition to the capacity to internalize into host cells, GAS strains have evolved a number of other mechanisms to avoid the host immune response. […] The rapid tissue destruction and bacterial spread are thought to involve host and bacterial proteases (plasmin, SpeB), spreading factors (e.g., phospholipase), and tissue-damaging enzymes released by host polymorphonuclear leukocytes in response to superantigens.

• #49 Pathogenesis, Virulence Factors, and Antibiotic Resistance of Group B Streptococcus | SpringerLink

  https://link.springer.com/chapter/10.1007/978-981-15-1695-5_8

  Streptococcus is an important genus in the gram-positive coccus, belonging to family Streptococcaceae. […] Group B Streptococcus is an opportunistic pathogenic bacteria causing severe neonatal sepsis, meningitis, bacteremia, urinary tract infections, endometritis, maternal bacteremia, and other associated diseases. […] The disease severity and chronic infection profile of GBS could be attributed to the presence of specific virulence determinants such as pore-forming toxins and capsular polysaccharides. […] The epidemiological profile of GBS gained considerable attention owing to its ability to exhibit resistance against conventional antibiotic treatment by forming recalcitrant biofilms. […] Despite the development in the therapeutic strategies to control GBS infections, the mortality and morbidity caused by GBS infections remain an uphill challenge for the scientific community.

• #50 Streptococcal Infections | Iowa State University

  https://vetmed.iastate.edu/vdpam/about/focus-areas/swine/swine-disease-manual/index-diseases/streptococcal-infection

  Pathogenesis is somewhat speculative and may differ among different serotypes. Management and husbandry stresses may predispose piglets to outbreaks. Also, preexisting injury to respiratory epithelium, especially rhinitis, may predispose to infection. Known causes of rhinitis include ammonia fumes, infection with Bordetella bronchiseptica and Pasteurella multocida, and inclusion body rhinitis. Interaction of S. suis with viruses (pseudorabies, swine influenza, porcine reproductive and respiratory syndrome [PRRS]) may trigger some outbreaks. […] After oral or respiratory entry, streptococci pass to the crypts of the palatine tonsils. From there the organisms invade via lymphatics to the mandibular lymph nodes where they can remain localized or become septicemic. Some organisms may survive within phagocytes and gain access to cerebrospinal fluid, brain, meninges, lungs and joints where they localize and cause meningoencephalitis, arthritis or pneumonia. In pneumonic lungs, S. suis can be either a primary or secondary pathogen.

• #51 Understanding streptococcal pathogenesis | Doherty Website

  https://www.doherty.edu.au/education/research-project/understanding-streptococcal-pathogenesis

  Streptococcus pyogenes (’Strep A’, group A streptococcus) is an important global pathogen. […] There is recent clinical epidemiologic evidence that viruses are also important in S. pyogenes pathogenesis, but little is known about this process. […] Your project will provide important novel data on key components of S. pyogenes pathogenesis and inform a pathway towards improving strategies for preventing S. pyogenes infections. […] We focus on the microbiology of pathogens of major global health importance (including pneumococcus and group A streptococcus) to understand their pathogenesis, interaction with viruses, and how infections can be best prevented with vaccines.

• #52 Streptococcus pyogenes – Wikipedia

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

  S. pyogeneshas several virulence factors that enable it to attach to host tissues, evade the immune response, and spread by penetrating host tissue layers. […] A carbohydrate-based bacterial capsule composed of hyaluronic acid surrounds the bacterium, protecting it from phagocytosis by neutrophils. […] In addition, the capsule and several factors embedded in the cell wall, including M protein, lipoteichoic acid, and protein F (SfbI) facilitate attachment to various host cells. […] M protein also inhibits opsonization by the alternative complement pathway by binding to host complement regulators. […] The M protein found on some serotypes is also able to prevent opsonization by binding to fibrinogen. […] However, the M protein is also the weakest point in this pathogen’s defense, as antibodies produced by the immune system against M protein target the bacteria for engulfment by phagocytes.

• #53 Streptococcus pyogenes – Wikipedia

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

  S. pyogeneshas several virulence factors that enable it to attach to host tissues, evade the immune response, and spread by penetrating host tissue layers. […] A carbohydrate-based bacterial capsule composed of hyaluronic acid surrounds the bacterium, protecting it from phagocytosis by neutrophils. […] In addition, the capsule and several factors embedded in the cell wall, including M protein, lipoteichoic acid, and protein F (SfbI) facilitate attachment to various host cells. […] M protein also inhibits opsonization by the alternative complement pathway by binding to host complement regulators. […] The M protein found on some serotypes is also able to prevent opsonization by binding to fibrinogen. […] However, the M protein is also the weakest point in this pathogen’s defense, as antibodies produced by the immune system against M protein target the bacteria for engulfment by phagocytes.

• #54 Azthena logo with the word Azthena

  https://www.news-medical.net/health/What-Causes-Strep-Throat.aspx

  Beta-hemolytic group A streptococcus or Streptococcus pyogenes, a gram-positive human pathogen that habitually colonizes the throat or skin of the host, is a cause of streptococcal pharyngitis more commonly known as strep throat. Infections with this microorganism are underpinned by a panoply of virulence factors that are produced in direct response to environmental signals in the host. […] Adherence and subsequent growth of Streptococcus pyogenes on pharyngeal mucosal surfaces are usually sufficient to cause the clinical entity of streptococcal pharyngitis. Adhering to epithelial cells is a prerequisite event in the disease pathogenesis, which is facilitated by fibronectin-binding protein or protein F (although M-protein and peptidoglycan may also contribute). […] Together with M-protein, think capsules formed of hyaluronic acid found in some strains of Streptococcus pyogenes confer resistance to phagocytosis. The microorganism can also stimulate T cell responses and cytokine induction, resulting in fever and further tissue injury. This can be especially important in the development of complications that can be provoked by certain strains of streptococci.

• #55 Pathogenesis of Group A Streptococcal Infections – Anna Henningham – Discovery Medicine

  https://www.discoverymedicine.com/Anna-Henningham/2012/05/16/pathogenesis-of-group-a-streptococcal-infections/

  Group A Streptococcus (GAS; Streptococcus pyogenes) is a Gram-positive human pathogen which typically colonizes the throat or skin of the host. […] GAS diseases are underpinned by an extensive repertoire of virulence determinants that are differentially regulated in direct response to a battery of environmental signals within the host. […] The trigger for rapidly progressive invasive GAS disease has also been linked to the capacity of GAS to hijack host molecules for redeployment as virulence factors. […] It is thought there are three stages in the pathogenesis of GAS pharyngitis: i) adherence to the host pharyngeal epithelial tissue, often followed by invasion into and persistence in host epithelial cells, ii) nutrient acquisition to enable proliferation in the host, and iii) evasion of the host immune response.

• #56 Pathogenesis of Group A Streptococcal Infections – Anna Henningham – Discovery Medicine

  https://www.discoverymedicine.com/Anna-Henningham/2012/05/16/pathogenesis-of-group-a-streptococcal-infections/

  Several adhesins and GAS molecules have been implicated in GAS adhesion to and invasion of host epithelial cells (both cutaneous and mucosal) including C5a peptidase, FbaA, FBP54, hyaluronic acid capsule, Lbp, Lsp, LTA, M protein, pili, Protein F1, Protein F2, SEN, SlaA, and SOF. […] Intracellular persistence of GAS has been linked to recurrent cases of pharyngitis and may potentially contribute to the failure of penicillin during treatment. […] In addition to the capacity to internalize into host cells, GAS strains have evolved a number of other mechanisms to avoid the host immune response. […] The rapid tissue destruction and bacterial spread are thought to involve host and bacterial proteases (plasmin, SpeB), spreading factors (e.g., phospholipase), and tissue-damaging enzymes released by host polymorphonuclear leukocytes in response to superantigens.

• #57 Pathogenesis of Group A Streptococcal Infections – Anna Henningham – Discovery Medicine

  https://www.discoverymedicine.com/Anna-Henningham/2012/05/16/pathogenesis-of-group-a-streptococcal-infections/

  Several adhesins and GAS molecules have been implicated in GAS adhesion to and invasion of host epithelial cells (both cutaneous and mucosal) including C5a peptidase, FbaA, FBP54, hyaluronic acid capsule, Lbp, Lsp, LTA, M protein, pili, Protein F1, Protein F2, SEN, SlaA, and SOF. […] Intracellular persistence of GAS has been linked to recurrent cases of pharyngitis and may potentially contribute to the failure of penicillin during treatment. […] In addition to the capacity to internalize into host cells, GAS strains have evolved a number of other mechanisms to avoid the host immune response. […] The rapid tissue destruction and bacterial spread are thought to involve host and bacterial proteases (plasmin, SpeB), spreading factors (e.g., phospholipase), and tissue-damaging enzymes released by host polymorphonuclear leukocytes in response to superantigens.

• #58 Pathogenesis of Group A Streptococcal Infections

  https://pmc.ncbi.nlm.nih.gov/articles/PMC88944/

  Group A streptococci are model extracellular gram-positive pathogens responsible for pharyngitis, impetigo, rheumatic fever, and acute glomerulonephritis. […] The strong resistance of the group A streptococcus to phagocytosis is related to factor H and fibrinogen binding by M protein and to disarming complement component C5a by the C5a peptidase. […] Molecular mimicry appears to play a role in autoimmune mechanisms involved in rheumatic fever, while nephritis strain-associated proteins may lead to immune-mediated acute glomerulonephritis. […] Several virulence factors of group A streptococci are likely to be involved in the pathogenesis of toxic shock, invasion of soft tissues and skin, and necrotizing fasciitis. […] The pyrogenic exotoxins are potentially responsible for at least some of the manifestations of toxic streptococcal syndrome.

• #59 Pathogenesis, epidemiology and control of Group A Streptococcus infection – PubMed

  https://pubmed.ncbi.nlm.nih.gov/36894668/

  Streptococcus pyogenes (Group A Streptococcus; GAS) is exquisitely adapted to the human host, resulting in asymptomatic infection, pharyngitis, pyoderma, scarlet fever or invasive diseases, with potential for triggering post-infection immune sequelae. GAS deploys a range of virulence determinants to allow colonization, dissemination within the host and transmission, disrupting both innate and adaptive immune responses to infection. […] The resulting tissue damage mounts a robust inflammatory response characterized by abundant infiltration of innate and adaptive immunity cells, attracted by various stimuli, such as human cathelicidin LL-37, pro-inflammatory cytokine interleukin-8 (IL-8) and SpeB-activated IL-36. […] GAS has evolved multiple mechanisms to elude the host immune system. These include the degradation of LL-37 by SpeB, IL-8 cleavage by S. pyogenes cell envelope proteinase (SpyCEP) and cleavage of the complement component 5a (C5a) by a C5a peptidase (ScpA). Coating of the bacterial surface with host factors, such as histones, plasminogen and fibrinogen, via binding to surface-expressed M protein further prevents immune recognition.

• #60 Pathogenesis, epidemiology and control of Group A Streptococcus infection | Nature Reviews Microbiology

  https://www.nature.com/articles/s41579-023-00865-7

  This study utilizes biomimetic virulomics to show that GAS S protein captures lysed red blood cell membranes to cloak the bacterial cell surface, which allows bacteria to evade host immunity. […] This comprehensive report demonstrates that M1 protein triggers caspase 1-dependent NLRP3 inflammasome activation, leading to pyroptotic macrophage cell death. […] This comprehensive report details the molecular basis of natural selection of hypervirulent bacterial variants with increased risk of systemic dissemination. […] This important study demonstrates that epithelial cytokine IL-36 is a global sensor of pathogen-derived proteases during epithelial infection. […] This work demonstrates how GAS exploits neuro-immunological signalling to cause invasive infection. […] This study uses a combination of in vitro evolution and metabolic rescue experiments to demonstrate that a new antimicrobial resistance mechanism undetectable using traditional laboratory testing methods is responsible for high levels of resistance to sulfamethoxazole in GAS.

• #61 How the strep bacterium hides from the immune system | ScienceDaily

  https://www.sciencedaily.com/releases/2019/12/191203114506.htm

  A bacterial pathogen that causes strep throat and other illnesses cloaks itself in fragments of red blood cells to evade detection by the host immune system, according to a new study. The researchers found that Group A Streptococcus (GAS) produces a previously uncharacterized protein, named S protein, which binds to the red blood cell membrane to avoid being engulfed and destroyed by phagocytic immune cells. […] By arming GAS with this form of immune camouflage, S protein enhances bacterial virulence and decreases survival in infected mice. […] „Our study describes a completely novel mechanism for immune evasion,” says corresponding author David Gonzalez of the University of California, San Diego. […] „These findings suggest that S protein co-opts red blood cell membranes for molecular mimicry, or imitation of host molecules, to evade the immune response,” Gonzalez says.

• #62 Pathogenesis of Group A Streptococcal Infections – Anna Henningham – Discovery Medicine

  https://www.discoverymedicine.com/Anna-Henningham/2012/05/16/pathogenesis-of-group-a-streptococcal-infections/

  The transition from superficial to invasive infection requires substantial changes in gene expression to facilitate bacterial evasion of sub-epithelial innate immune functions and dissemination into deeper tissues. […] Invasive GAS also produces increased levels of multiple toxins, including cytotoxins (streptolysin O, NAD glycohydrolase) and superantigens (e.g., SpeA, SpeJ), which destroy immune cells and dysregulate the hosts immune response, respectively. […] The changes in gene expression by invasive GAS has been shown to occur by a novel mechanism that involves the accumulation of mutations in a two-component signal transduction system, CovR/S. […] Thus, the transition of GAS to cause invasive disease is potentially triggered by the host innate immune system, providing selective pressure for mutations that result in increased expression of a quorum of GAS virulence factors that convey resistance to neutrophil-mediated killing.

• #63 Pathogenesis of Group A Streptococcal Infections – Anna Henningham – Discovery Medicine

  https://www.discoverymedicine.com/Anna-Henningham/2012/05/16/pathogenesis-of-group-a-streptococcal-infections/

  The transition from superficial to invasive infection requires substantial changes in gene expression to facilitate bacterial evasion of sub-epithelial innate immune functions and dissemination into deeper tissues. […] Invasive GAS also produces increased levels of multiple toxins, including cytotoxins (streptolysin O, NAD glycohydrolase) and superantigens (e.g., SpeA, SpeJ), which destroy immune cells and dysregulate the hosts immune response, respectively. […] The changes in gene expression by invasive GAS has been shown to occur by a novel mechanism that involves the accumulation of mutations in a two-component signal transduction system, CovR/S. […] Thus, the transition of GAS to cause invasive disease is potentially triggered by the host innate immune system, providing selective pressure for mutations that result in increased expression of a quorum of GAS virulence factors that convey resistance to neutrophil-mediated killing.

• #64 Pathogenesis of Group A Streptococcal Infections – Anna Henningham – Discovery Medicine

  https://www.discoverymedicine.com/Anna-Henningham/2012/05/16/pathogenesis-of-group-a-streptococcal-infections/

  The transition from superficial to invasive infection requires substantial changes in gene expression to facilitate bacterial evasion of sub-epithelial innate immune functions and dissemination into deeper tissues. […] Invasive GAS also produces increased levels of multiple toxins, including cytotoxins (streptolysin O, NAD glycohydrolase) and superantigens (e.g., SpeA, SpeJ), which destroy immune cells and dysregulate the hosts immune response, respectively. […] The changes in gene expression by invasive GAS has been shown to occur by a novel mechanism that involves the accumulation of mutations in a two-component signal transduction system, CovR/S. […] Thus, the transition of GAS to cause invasive disease is potentially triggered by the host innate immune system, providing selective pressure for mutations that result in increased expression of a quorum of GAS virulence factors that convey resistance to neutrophil-mediated killing.

• #65 Pathogenesis of Group A Streptococcal Infections – Anna Henningham – Discovery Medicine

  https://www.discoverymedicine.com/Anna-Henningham/2012/05/16/pathogenesis-of-group-a-streptococcal-infections/

  The transition from superficial to invasive infection requires substantial changes in gene expression to facilitate bacterial evasion of sub-epithelial innate immune functions and dissemination into deeper tissues. […] Invasive GAS also produces increased levels of multiple toxins, including cytotoxins (streptolysin O, NAD glycohydrolase) and superantigens (e.g., SpeA, SpeJ), which destroy immune cells and dysregulate the hosts immune response, respectively. […] The changes in gene expression by invasive GAS has been shown to occur by a novel mechanism that involves the accumulation of mutations in a two-component signal transduction system, CovR/S. […] Thus, the transition of GAS to cause invasive disease is potentially triggered by the host innate immune system, providing selective pressure for mutations that result in increased expression of a quorum of GAS virulence factors that convey resistance to neutrophil-mediated killing.

• #66 Pathogenesis of Group A Streptococcal Infections – Anna Henningham – Discovery Medicine

  https://www.discoverymedicine.com/Anna-Henningham/2012/05/16/pathogenesis-of-group-a-streptococcal-infections/

  Several adhesins and GAS molecules have been implicated in GAS adhesion to and invasion of host epithelial cells (both cutaneous and mucosal) including C5a peptidase, FbaA, FBP54, hyaluronic acid capsule, Lbp, Lsp, LTA, M protein, pili, Protein F1, Protein F2, SEN, SlaA, and SOF. […] Intracellular persistence of GAS has been linked to recurrent cases of pharyngitis and may potentially contribute to the failure of penicillin during treatment. […] In addition to the capacity to internalize into host cells, GAS strains have evolved a number of other mechanisms to avoid the host immune response. […] The rapid tissue destruction and bacterial spread are thought to involve host and bacterial proteases (plasmin, SpeB), spreading factors (e.g., phospholipase), and tissue-damaging enzymes released by host polymorphonuclear leukocytes in response to superantigens.

• #67 Pathogenesis of Group A Streptococcal Infections

  https://pmc.ncbi.nlm.nih.gov/articles/PMC88944/

  Group A streptococci are model extracellular gram-positive pathogens responsible for pharyngitis, impetigo, rheumatic fever, and acute glomerulonephritis. […] The strong resistance of the group A streptococcus to phagocytosis is related to factor H and fibrinogen binding by M protein and to disarming complement component C5a by the C5a peptidase. […] Molecular mimicry appears to play a role in autoimmune mechanisms involved in rheumatic fever, while nephritis strain-associated proteins may lead to immune-mediated acute glomerulonephritis. […] Several virulence factors of group A streptococci are likely to be involved in the pathogenesis of toxic shock, invasion of soft tissues and skin, and necrotizing fasciitis. […] The pyrogenic exotoxins are potentially responsible for at least some of the manifestations of toxic streptococcal syndrome.

• #68 Rheumatic fever – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/rheumatic-fever/symptoms-causes/syc-20354588

  Rheumatic fever can happen after a throat infection from group A streptococcus bacteria, also called strep bacteria. The bacteria cause strep throat and scarlet fever. Improperly treated strep throat or scarlet fever infections cause rheumatic fever. […] How a strep infection causes rheumatic fever isn’t clear. It may be that the bacteria trick the body’s immune system into attacking healthy tissue. This usually happens in the heart, joints, skin and central nervous system. The incorrect immune system reaction causes swelling of joints and tissues. This swelling is called inflammation.

• #69 Rheumatic fever – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/rheumatic-fever/symptoms-causes/syc-20354588

  Rheumatic fever can happen after a throat infection from group A streptococcus bacteria, also called strep bacteria. The bacteria cause strep throat and scarlet fever. Improperly treated strep throat or scarlet fever infections cause rheumatic fever. […] How a strep infection causes rheumatic fever isn’t clear. It may be that the bacteria trick the body’s immune system into attacking healthy tissue. This usually happens in the heart, joints, skin and central nervous system. The incorrect immune system reaction causes swelling of joints and tissues. This swelling is called inflammation.

• #70 Azthena logo with the word Azthena

  https://www.news-medical.net/health/What-Causes-Strep-Throat.aspx

  The immunological response of the host to streptococcal infection is characterized by the production of antibodies against a myriad of streptococcal cellular and extracellular constituents. Host responses against the aforementioned M-protein serotype can protect from reinfection with that specific serotype.

• #71 Pathogenesis of Group A Streptococcal Infections

  https://pmc.ncbi.nlm.nih.gov/articles/PMC88944/

  The pathogenic events that lead to the development of poststreptococcal acute glomerulonephritis are related to an immunologic phenomenon involving immune complexes, nephritogenic streptococcal proteins, or both. […] The nephritogenicity of group A streptococci appears to be related to specific M protein serotypes of S. pyogenes which cause acute glomerulonephritis, and certain strains within the serotype are nephritogenic. […] The pathogenic mechanisms involved in poststreptococcal sequelae.

• #72 Pathogenesis of Group A Streptococcal Infections

  https://pmc.ncbi.nlm.nih.gov/articles/PMC88944/

  The pathogenic events that lead to the development of poststreptococcal acute glomerulonephritis are related to an immunologic phenomenon involving immune complexes, nephritogenic streptococcal proteins, or both. […] The nephritogenicity of group A streptococci appears to be related to specific M protein serotypes of S. pyogenes which cause acute glomerulonephritis, and certain strains within the serotype are nephritogenic. […] The pathogenic mechanisms involved in poststreptococcal sequelae.

• #73 Pathogenesis of Group A Streptococcal Infections

  https://pmc.ncbi.nlm.nih.gov/articles/PMC88944/

  Group A streptococci are model extracellular gram-positive pathogens responsible for pharyngitis, impetigo, rheumatic fever, and acute glomerulonephritis. […] The strong resistance of the group A streptococcus to phagocytosis is related to factor H and fibrinogen binding by M protein and to disarming complement component C5a by the C5a peptidase. […] Molecular mimicry appears to play a role in autoimmune mechanisms involved in rheumatic fever, while nephritis strain-associated proteins may lead to immune-mediated acute glomerulonephritis. […] Several virulence factors of group A streptococci are likely to be involved in the pathogenesis of toxic shock, invasion of soft tissues and skin, and necrotizing fasciitis. […] The pyrogenic exotoxins are potentially responsible for at least some of the manifestations of toxic streptococcal syndrome.

• #74 Pathogenesis of Group A Streptococcal Infections

  https://pmc.ncbi.nlm.nih.gov/articles/PMC88944/

  Group A streptococci are model extracellular gram-positive pathogens responsible for pharyngitis, impetigo, rheumatic fever, and acute glomerulonephritis. […] The strong resistance of the group A streptococcus to phagocytosis is related to factor H and fibrinogen binding by M protein and to disarming complement component C5a by the C5a peptidase. […] Molecular mimicry appears to play a role in autoimmune mechanisms involved in rheumatic fever, while nephritis strain-associated proteins may lead to immune-mediated acute glomerulonephritis. […] Several virulence factors of group A streptococci are likely to be involved in the pathogenesis of toxic shock, invasion of soft tissues and skin, and necrotizing fasciitis. […] The pyrogenic exotoxins are potentially responsible for at least some of the manifestations of toxic streptococcal syndrome.

• #75 Group A Strep | Caparon Lab | Washington University in St. Louis

  https://caparonlab.wustl.edu/group-a-strep/

  Three streptococcal pyrogenic exotoxins (SPE), formerly known as Erythrogenic toxin, are recognized: types A, B, C. These toxins act as superantigens by a mechanism similar to those described for staphylococci. […] The destructive nature of wound infections prompted the popular press to refer to S. pyogenes as flesh-eating bacteria and ski-eating streptococci. The increase in invasive streptococcal disease was associated with emergence of a highly virulent serotype M1 which is disseminated worldwide.

• #76 Streptococcal toxic shock syndrome in the intensive care unit | Annals of Intensive Care | Full Text

  https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-018-0438-y

  The exact mechanism of STSS is not entirely understood but has to do with a combination of the effect of streptococcal toxinsenterotoxins with superantigen activityother streptococcal enzymes and toxins, and the host response to streptococcal infection, a complex interplay between host immunity and pathogen virulence. […] The pathophysiology of STSS is based on bacterial toxins. Superantigens are proteins that share the ability to trigger excessive and nonspecific T cell activation, therefore generating the massive secretion pro-inflammatory cytokines and other mediators producing capillary leak and arterial hypotension. […] Staphylococci and streptococci are the two most common bacterial genera known to produce superantigens. Among streptococci, Streptococcus pyogenes (group A streptococcus), S. dysgalactiae (group C streptococcus), and S. equis (group G streptococcus) can produce exotoxins with superantigen activity.

• #77 Streptococcal toxic shock syndrome in the intensive care unit | Annals of Intensive Care | Full Text

  https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-018-0438-y

  The exact mechanism of STSS is not entirely understood but has to do with a combination of the effect of streptococcal toxinsenterotoxins with superantigen activityother streptococcal enzymes and toxins, and the host response to streptococcal infection, a complex interplay between host immunity and pathogen virulence. […] The pathophysiology of STSS is based on bacterial toxins. Superantigens are proteins that share the ability to trigger excessive and nonspecific T cell activation, therefore generating the massive secretion pro-inflammatory cytokines and other mediators producing capillary leak and arterial hypotension. […] Staphylococci and streptococci are the two most common bacterial genera known to produce superantigens. Among streptococci, Streptococcus pyogenes (group A streptococcus), S. dysgalactiae (group C streptococcus), and S. equis (group G streptococcus) can produce exotoxins with superantigen activity.

• #78 Streptococcal toxic shock syndrome in the intensive care unit | Annals of Intensive Care | Full Text

  https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-018-0438-y

  The main characteristic of superantigens is their ability to bind to major histocompatibility (MHC) class II molecules outside of the antigen groove, and the V region of the T cell receptor, cross-linking those two receptors. This triggers the activation of both the antigen-presenting cell and the T lymphocyte, bypassing conventional mechanisms of MHC-limited antigen cell activation. […] Aside from superantigens, S. pyogenes produces and secretes a wide variety of exotoxins and enzymes such as streptolysins, streptokinase, hyaluronidase, and DNAse such as streptodornase and chemokine proteases and toxic molecules that play undoubtedly an important pathogenic role in necrotizing fasciitis and STSS. […] Preexisting skin lesions are the most frequently identified risk factor for invasive GAS infection. Alcohol abuse, chronic lung disease, immunosuppression, intravenous drug use, heart disease, diabetes, cancer, varicella zoster virus infection, and recent child birth have also been identified as risk factors.

• #79 Streptococcal toxic shock syndrome in the intensive care unit | Annals of Intensive Care | Full Text

  https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-018-0438-y

  Interestingly, it has been demonstrated that MHC class II haplotypes influence the host susceptibility to develop STSS. The haplotype DR15/DQ6 is less commonly associated with STSS disease than the haplotype DR14/DQ5, for example. […] Retrospective studies and case series describe the possible association between nonsteroidal anti-inflammatory drugs (NSAIDs) use and the development and/or the extension of serious invasive diseases due to GAS. […] The association could also be that NSAIDs use in invasive GAS infection may mask initial signs and symptoms, and delay diagnosis and adapted treatment of invasive infections. Others have argued though that NSAIDs is independently associated with an increased risk for development of streptococcal toxic shock syndrome.

• #80 Pathogenesis, epidemiology and control of Group A Streptococcus infection | Nature Reviews Microbiology

  https://www.nature.com/articles/s41579-023-00865-7

  Streptococcus pyogenes (Group A Streptococcus; GAS) is exquisitely adapted to the human host, resulting in asymptomatic infection, pharyngitis, pyoderma, scarlet fever or invasive diseases, with potential for triggering post-infection immune sequelae. […] GAS deploys a range of virulence determinants to allow colonization, dissemination within the host and transmission, disrupting both innate and adaptive immune responses to infection. […] The recent identification of clinical GAS isolates with reduced penicillin sensitivity and increasing macrolide resistance threatens both frontline and penicillin-adjunctive antibiotic treatment. […] This paper reports demonstrating that SpeB triggers keratinocyte pyroptosis by cleaving GSDMA, providing a mechanism for inflammatory response stimulation at the epithelial cell layer.

• #81 New Antimicrobial Resistance Mechanism Discovered in Streptococci

  https://www.genengnews.com/news/new-antimicrobial-resistance-mechanism-discovered-in-streptococci/

  Bacteria use a variety of mechanisms to render antimicrobials ineffective: efflux pumps that remove compounds from the cell, enzymatic degradation of an antimicrobial compound, and modification of a target are some examples that are widely used. […] Now, a new form of AMR—one that is undetectable using traditional laboratory testing methods—has been uncovered. The mechanism, which requires a host metabolite for activity, enables Group A Streptococcus to take up nutrients from their human host and confer sulfamethoxazole resistance. More specifically, the bacteria acquire extracellular reduced folate compounds directly from the host in order to bypass the inhibition of folate biosynthesis by sulfamethoxazole. […] More specifically, the findings identify an energy-coupling factor (ECF) transporter S component gene (thfT) that enables Group A Streptococcus to acquire extracellular reduced folate compounds. ThfT, they note, likely “expands the substrate specificity of an endogenous ECF transporter to acquire reduced folate compounds directly from the host, thereby bypassing the inhibition of folate biosynthesis by sulfamethoxazole.”

• #82 New Antimicrobial Resistance Mechanism Discovered in Streptococci

  https://www.genengnews.com/news/new-antimicrobial-resistance-mechanism-discovered-in-streptococci/

  Bacteria use a variety of mechanisms to render antimicrobials ineffective: efflux pumps that remove compounds from the cell, enzymatic degradation of an antimicrobial compound, and modification of a target are some examples that are widely used. […] Now, a new form of AMR—one that is undetectable using traditional laboratory testing methods—has been uncovered. The mechanism, which requires a host metabolite for activity, enables Group A Streptococcus to take up nutrients from their human host and confer sulfamethoxazole resistance. More specifically, the bacteria acquire extracellular reduced folate compounds directly from the host in order to bypass the inhibition of folate biosynthesis by sulfamethoxazole. […] More specifically, the findings identify an energy-coupling factor (ECF) transporter S component gene (thfT) that enables Group A Streptococcus to acquire extracellular reduced folate compounds. ThfT, they note, likely “expands the substrate specificity of an endogenous ECF transporter to acquire reduced folate compounds directly from the host, thereby bypassing the inhibition of folate biosynthesis by sulfamethoxazole.”

• #83 New Antimicrobial Resistance Mechanism Discovered in Streptococci

  https://www.genengnews.com/news/new-antimicrobial-resistance-mechanism-discovered-in-streptococci/

  Bacteria use a variety of mechanisms to render antimicrobials ineffective: efflux pumps that remove compounds from the cell, enzymatic degradation of an antimicrobial compound, and modification of a target are some examples that are widely used. […] Now, a new form of AMR—one that is undetectable using traditional laboratory testing methods—has been uncovered. The mechanism, which requires a host metabolite for activity, enables Group A Streptococcus to take up nutrients from their human host and confer sulfamethoxazole resistance. More specifically, the bacteria acquire extracellular reduced folate compounds directly from the host in order to bypass the inhibition of folate biosynthesis by sulfamethoxazole. […] More specifically, the findings identify an energy-coupling factor (ECF) transporter S component gene (thfT) that enables Group A Streptococcus to acquire extracellular reduced folate compounds. ThfT, they note, likely “expands the substrate specificity of an endogenous ECF transporter to acquire reduced folate compounds directly from the host, thereby bypassing the inhibition of folate biosynthesis by sulfamethoxazole.”

• #84 New Antimicrobial Resistance Mechanism Discovered in Streptococci

  https://www.genengnews.com/news/new-antimicrobial-resistance-mechanism-discovered-in-streptococci/

  Bacteria use a variety of mechanisms to render antimicrobials ineffective: efflux pumps that remove compounds from the cell, enzymatic degradation of an antimicrobial compound, and modification of a target are some examples that are widely used. […] Now, a new form of AMR—one that is undetectable using traditional laboratory testing methods—has been uncovered. The mechanism, which requires a host metabolite for activity, enables Group A Streptococcus to take up nutrients from their human host and confer sulfamethoxazole resistance. More specifically, the bacteria acquire extracellular reduced folate compounds directly from the host in order to bypass the inhibition of folate biosynthesis by sulfamethoxazole. […] More specifically, the findings identify an energy-coupling factor (ECF) transporter S component gene (thfT) that enables Group A Streptococcus to acquire extracellular reduced folate compounds. ThfT, they note, likely “expands the substrate specificity of an endogenous ECF transporter to acquire reduced folate compounds directly from the host, thereby bypassing the inhibition of folate biosynthesis by sulfamethoxazole.”

• #85 New Antimicrobial Resistance Mechanism Discovered in Streptococci

  https://www.genengnews.com/news/new-antimicrobial-resistance-mechanism-discovered-in-streptococci/

  The authors continued that “ThfT is a functional equivalent of eukaryotic folate uptake pathways that confers very high levels of resistance to sulfamethoxazole, yet remains undetectable when Group A Streptococcus is grown in the absence of reduced folates.” […] Because the new form of resistance is undetectable under conditions routinely used in pathology laboratories, it is very hard for clinicians to prescribe antibiotics that will effectively treat the infection, potentially leading to very poor outcomes and even premature death. […] “Unfortunately, we suspect this is just the tip of the iceberg,” noted Barnett. “We have identified this mechanism in Group A Strep but it’s likely it will be a broader issue across other bacterial pathogens.” […] The team will now focus on developing testing methods to detect this antibiotic resistance mechanism to enable effective treatment.

• #86 Integrated analysis of population genomics, transcriptomics and virulence provides novel insights into Streptococcus pyogenes pathogenesis | Nature Genetics

  https://www.nature.com/articles/s41588-018-0343-1

  Streptococcus pyogenes causes 700 million human infections annually worldwide, yet, despite a century of intensive effort, there is no licensed vaccine against this bacterium. […] Data integration provided a novel understanding of the virulence mechanisms of this model organism. […] Genome-wide association study, expression quantitative trait loci analysis, machine learning, and isogenic mutant strains identified and confirmed a one-nucleotide indel in an intergenic region that significantly alters global transcript profiles and ultimately virulence. […] The integrative strategy that we used is generally applicable to any microbe and may lead to new therapeutics for many human pathogens. […] An intergenic single-nucleotide insertion increases Spy1336/R28 expression and strain virulence.

• #87

  https://step1.medbullets.com/evidence/22642914

  Group A Streptococcus (GAS; Streptococcus pyogenes) is a human pathogen which causes significant morbidity and mortality globally. GAS typically infects the throat and skin of the host, causing mild infections such as pharyngitis and impetigo, in addition to life threatening conditions including necrotizing fasciitis, streptococcal toxic shock syndrome (STSS), and bacteremia. […] Repeated infection with GAS may result in the non-suppurative sequelae, acute rheumatic fever, and acute glomerulonephritis. […] A vaccine capable of preventing GAS infection may be the only effective way to control and eliminate GAS infection and disease.

• #88 How the strep bacterium hides from the immune system | ScienceDaily

  https://www.sciencedaily.com/releases/2019/12/191203114506.htm

  „Taken together, the results suggest that inactivation of S protein function makes GAS vulnerable to host immunity,” Gonzalez says. „S protein influences virulence by capturing lysed red blood cell membranes to cloak the bacterial cell surface, which allows bacteria to circumvent host immunity. This novel evasion mechanism can be targeted for anti-streptococcal therapies.” […] „Ultimately, the findings could lead to the development of a novel vaccine candidate,” Gonzalez says. „Because of its pivotal roles in pathogenesis and immune evasion, and its conserved nature in Streptococci, S protein shows promising clinical potential as a target for the development of anti-virulence pharmacological interventions.”

• #89 Bacterial Pathogenesis

  https://pediatrics.ucsd.edu/research/faculty-labs/nizet-lab/research/bacterial-pathogenesis.html

  Group A Streptococcus (GAS) is an important human pathogen causing diseases ranging from simple pharyngitis („strep throat”) to invasive necrotizing fasciitis („flesh-eating disease”) to the immune-mediated syndrome of rheumatic fever. […] Of particular interest are genetic mechanisms of GAS innate immune resistance and the shift from mucosal colonization to systemic disease. […] Among the GAS virulence factors we study are the pore-forming toxins streptolysins S and O (SLS and SLO), the antiphagocytic and proinflammatory surface M protein, DNAse Sda1, cysteine protease SpeB, hyaluronic acid capsule, serum opacity factor, IL-8 peptidase, and the cell wall group A carbohydrate. […] Together, these studies aim to provide new targets for drug therapy and vaccine prophylaxis.

• #90 Integrated analysis of population genomics, transcriptomics and virulence provides novel insights into Streptococcus pyogenes pathogenesis | Nature Genetics

  https://www.nature.com/articles/s41588-018-0343-1

  Streptococcus pyogenes causes 700 million human infections annually worldwide, yet, despite a century of intensive effort, there is no licensed vaccine against this bacterium. […] Data integration provided a novel understanding of the virulence mechanisms of this model organism. […] Genome-wide association study, expression quantitative trait loci analysis, machine learning, and isogenic mutant strains identified and confirmed a one-nucleotide indel in an intergenic region that significantly alters global transcript profiles and ultimately virulence. […] The integrative strategy that we used is generally applicable to any microbe and may lead to new therapeutics for many human pathogens. […] An intergenic single-nucleotide insertion increases Spy1336/R28 expression and strain virulence.

• #91 Integrated analysis of population genomics, transcriptomics and virulence provides novel insights into Streptococcus pyogenes pathogenesis | Nature Genetics

  https://www.nature.com/articles/s41588-018-0343-1

  Streptococcus pyogenes causes 700 million human infections annually worldwide, yet, despite a century of intensive effort, there is no licensed vaccine against this bacterium. […] Data integration provided a novel understanding of the virulence mechanisms of this model organism. […] Genome-wide association study, expression quantitative trait loci analysis, machine learning, and isogenic mutant strains identified and confirmed a one-nucleotide indel in an intergenic region that significantly alters global transcript profiles and ultimately virulence. […] The integrative strategy that we used is generally applicable to any microbe and may lead to new therapeutics for many human pathogens. […] An intergenic single-nucleotide insertion increases Spy1336/R28 expression and strain virulence.

• #92 Integrated analysis of population genomics, transcriptomics and virulence provides novel insights into Streptococcus pyogenes pathogenesis | Nature Genetics

  https://www.nature.com/articles/s41588-018-0343-1

  Streptococcus pyogenes causes 700 million human infections annually worldwide, yet, despite a century of intensive effort, there is no licensed vaccine against this bacterium. […] Data integration provided a novel understanding of the virulence mechanisms of this model organism. […] Genome-wide association study, expression quantitative trait loci analysis, machine learning, and isogenic mutant strains identified and confirmed a one-nucleotide indel in an intergenic region that significantly alters global transcript profiles and ultimately virulence. […] The integrative strategy that we used is generally applicable to any microbe and may lead to new therapeutics for many human pathogens. […] An intergenic single-nucleotide insertion increases Spy1336/R28 expression and strain virulence.

Zobacz więcej