Molecular basis of group A streptococcal virulence

Bisno, Alan L.; Brito, Maximo O.; Collins, Carleen

doi:10.1016/s1473-3099(03)00576-0

Cited by 439 publications

(344 citation statements)

References 134 publications

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“…The heterogeneity of GAS diseases arises in part from the high diversity of GAS-mediated host-pathogen interactions in which virulence factors, GAS genome composition, prophage DNA, and plasticity of the GAS transcriptome play key roles (2,(61)(62)(63)(64). A major factor influencing the severity of GAS infections is also the genetic inventory of the host.…”

Section: Discussionmentioning

confidence: 99%

Group A Streptococcus Activates Type I Interferon Production and MyD88-dependent Signaling without Involvement of TLR2, TLR4, and TLR9

Gratz

Siller

Schaljo

et al. 2008

Journal of Biological Chemistry

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Bacterial pathogens are recognized by the innate immune system through pattern recognition receptors, such as Toll-like receptors (TLRs). Engagement of TLRs triggers signaling cascades that launch innate immune responses. Activation ofMAPKs and NF-B, elements of the major signaling pathways induced by TLRs, depends in most cases on the adaptor molecule MyD88. In addition, Gram-negative or intracellular bacteria elicit MyD88-independent signaling that results in production of type I interferon (IFN). Here we show that in mouse macrophages, the activation of MyD88-dependent signaling by the extracellular Gram-positive human pathogen group A streptococcus (GAS; Streptococcus pyogenes) does not require TLR2, a receptor implicated in sensing of Gram-positive bacteria, or TLR4 and TLR9. Redundant engagement of either of these TLR molecules was excluded by using TLR2/4/9 triple-deficient macrophages. We further demonstrate that infection of macrophages by GAS causes IRF3 (interferon-regulatory factor 3)-dependent, MyD88-independent production of IFN. Surprisingly, IFN is induced also by GAS lacking slo and sagA, the genes encoding cytolysins that were shown to be required for IFN production in response to other Gram-positive bacteria. Our data indicate that (i) GAS is recognized by a MyD88-dependent receptor other than any of those typically used by bacteria, and (ii) GAS as well as GAS mutants lacking cytolysin genes induce type I IFN production by similar mechanisms as bacteria requiring cytoplasmic escape and the function of cytolysins.Group A streptococcus (GAS 4 ; Streptococcus pyogenes) is an important human Gram-positive pathogen responsible for a wide spectrum of infections, ranging from mild diseases (e.g. tonsillitis) to serious illness (e.g. necrotizing fasciitis, sepsis, or severe poststreptococcal sequelae) (1). The persistence of GAS in the human population and the severity of some GAS diseases are the result of activities of a number of virulence factors that enable the pathogen to escape immune surveillance or, on contrary, induce an overreaction of the immune system (2, 3). Although GAS is generally regarded as an extracellular pathogen, recent findings suggest that GAS can survive (although not multiply) within various host cells, such as neutrophils, macrophages, epithelial cells, and fibroblasts (4 -7). The surviving bacteria may serve as a reservoir for recurrent GAS diseases.Immune responses to bacteria are initiated by recognition of bacterial components called pathogen-associated molecular patterns through host cell-encoded pattern recognition receptors (PRRs) (8, 9). Typically, pathogen-associated molecular patterns are components of the bacterial cell wall (e.g. lipopolysaccharide and lipoteichoic acid), but they may also be derived from the inside of bacteria (e.g. DNA). The primary function of PRRs is to trigger signaling cascades that activate antimicrobial defense programs. The best studied class of PRRs is the Toll-like receptor (TLR) family, which consists of 13 transmembrane glycoprote...

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Section: Discussionmentioning

confidence: 99%

Group A Streptococcus Activates Type I Interferon Production and MyD88-dependent Signaling without Involvement of TLR2, TLR4, and TLR9

Gratz

Siller

Schaljo

et al. 2008

Journal of Biological Chemistry

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“…However, studies have previously shown that there are almost no first-line immune defense cells, such as macrophages and neutrophils, in serious GAS infections. 4,5 These studies suggested that survival and multiplication of GAS might utilize a novel strategy to combat host innate and adaptive immunity.…”

Section: Introductionmentioning

confidence: 99%

A MyD88–JAK1–STAT1 complex directly induces SOCS-1 expression in macrophages infected with Group A Streptococcus

Wang

et al. 2014

Cell Mol Immunol

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Some pathogens can use host suppressor of cytokine signaling 1 (SOCS-1), an important negative-feedback molecule, as the main mode of immune evasion. Here we found that group A Streptococcus (GAS) is capable of inducing SOCS-1 expression in RAW264.7 and BMDM macrophages. IFN-b plays a role in GAS-induced SOCS-1 expression in macrophages following the induction of cytokine expression by GAS, representing the classical pathway of SOCS-1 expression. However, GAS also induced STAT1 activation and SOCS-1 expression when GAS-infected cells were incubated with anti-IFN-b monoclonal antibody in this study. Moreover, upon comparing TLR4 2/2 BMDM macrophages with wild-type (WT) cells, we found that TLR4 also plays an essential role in the induction of SOCS-1. MyD88, which is an adaptor protein for TLR4, contributes to STAT1 activation and phosphorylation by forming a complex with Janus kinase 1 (JAK1) and signal transducer and activator of transcription 1 (STAT1) in macrophages. GAS-stimulated expression of STAT1 was severely impaired in MyD88 2/2 macrophages, whereas expression of JAK1 was unaffected, suggesting that MyD88 was involved in STAT1 expression and phosphorylation. Together, these data demonstrated that in addition to IFN-b signaling and MyD88 complex formation, JAK1 and STAT1 act in a novel pathway to directly induce SOCS-1 expression in GAS-infected macrophages, which may be more conducive to rapid bacterial infection.

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“…Cases of infections with Staphylococcus aureus resistant to a wide range of antibacterial abound today. [6][7][8] Streptococcus is a genus of spherical Gram-positive facultative anaerobic bacteria of the phylum Finicutes and the lactic acid group. Pathogenic streptococci are classified as α, β or ∂-hemolytic organisms based on their hemolytic properties.…”

Section: Introductionmentioning

confidence: 99%

Consumption of Antibacterial Within the Southern Nigerian Population: Sources, Pattern and Appropriateness in Respiratory Tract Infection

Olajide

Eyen

Jimmy

2011

Int J of Biomed & Adv Res

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The study was designed to assess the sources and pattern of procurement, knowledge and attitude of consumers of antibacterial agents and the appropriateness of use in respect of respiratory tract infections. Buyers at the point of purchase were interviewed with a structured questionnaire. 65 respondents were randomly selected among buyers who had duly signed prescriptions but without prior laboratory tests. Sputum samples were collected for microbiology, culture and sensitivity to match up for appropriateness with requested antibacterial. 40 % of the study population believed that laboratory test was not required before the use of antibacterial. 27% of the respondents have tertiary education and only 4% have a monthly income in excess of N100, 000 (

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Molecular basis of group A streptococcal virulence

Cited by 439 publications

References 134 publications

Group A Streptococcus Activates Type I Interferon Production and MyD88-dependent Signaling without Involvement of TLR2, TLR4, and TLR9

Group A Streptococcus Activates Type I Interferon Production and MyD88-dependent Signaling without Involvement of TLR2, TLR4, and TLR9

A MyD88–JAK1–STAT1 complex directly induces SOCS-1 expression in macrophages infected with Group A Streptococcus

Consumption of Antibacterial Within the Southern Nigerian Population: Sources, Pattern and Appropriateness in Respiratory Tract Infection

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