Superantigen Genes Are More Important than the<i>emm</i>Type for the Invasiveness of Group A<i>Streptococcus</i>Infection

Lintges, Maria; Linden, Mark van der; Hilgers, Ralf-Dieter; Arlt, Sabine; Al‐Lahham, Adnan; Reinert, Ralf René; Plücken, Stefan; Rink, Lothar

doi:10.1086/653082

Cited by 46 publications

(43 citation statements)

References 54 publications

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“…Our study did suggest a significant association between infections caused by emm1 and severe disease, whereas patients with emm89 and 12 had less severe disease courses. The reasons why certain emm types are capable of causing more severe disease is unknown, but may be related to their associations with yet another virulence trait, such as production of SpeA, SpeZ and SpeJ exotoxins [30]. However, no correlation between clinical manifestations and a single superantigen gene in GAS has been found [11].…”

Section: Discussionmentioning

confidence: 99%

Invasive infections due to Streptococcus pyogenes: seasonal variation of severity and clinical characteristics, Iceland, 1975 to 2012

et al. 2014

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Section: Discussionmentioning

confidence: 99%

Invasive infections due to Streptococcus pyogenes: seasonal variation of severity and clinical characteristics, Iceland, 1975 to 2012

et al. 2014

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“…This observation has stimulated study of the genetic basis for differences in virulence among strains of the same bacterial species, which has generally focused on the effect of diversity in gene content (4)(5)(6)(7). However, for many important bacterial pathogens it is clear that variation in gene content is insufficient to explain all virulence differences between strains (8-10).…”

Section: Introductionmentioning

confidence: 99%

Naturally occurring single amino acid replacements in a regulatory protein alter streptococcal gene expression and virulence in mice

Carroll¹,

Shelburne²,

Olsen³

et al. 2011

J. Clin. Invest.

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Infection with different strains of the same species of bacteria often results in vastly different clinical outcomes. Despite extensive investigation, the genetic basis of microbial strain-specific virulence remains poorly understood. Recent whole-genome sequencing has revealed that SNPs are the most prevalent form of genetic diversity among different strains of the same species of bacteria. For invasive serotype M3 group A streptococci (GAS) strains, the gene encoding regulator of proteinase B (RopB) has the highest frequency of SNPs. Here, we have determined that ropB polymorphisms alter RopB function and modulate GAS host-pathogen interactions. Sequencing of ropB in 171 invasive serotype M3 GAS strains identified 19 distinct ropB alleles. Inactivation of the ropB gene in strains producing distinct RopB variants had dramatically divergent effects on GAS global gene expression. Additionally, generation of isoallelic GAS strains differing only by a single amino acid in RopB confirmed that variant proteins affected transcript levels of the gene encoding streptococcal proteinase B, a major RopB-regulated virulence factor. Comparison of parental, RopB-inactivated, and RopB isoallelic strains in mouse infection models demonstrated that ropB polymorphisms influence GAS virulence and disease manifestations. These data detail a paradigm in which unbiased, whole-genome sequence analysis of populations of clinical bacterial isolates creates new avenues of productive investigation into the pathogenesis of common human infections.

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“…The GAS superantigens (SAgs) are also important for virulence, participating in the induction of the systemic toxicity associated with severe infections [14][15][16]. Currently, at least 11 distinct streptococcal SAgs are known, including the streptococcal pyrogenic exotoxins (Spe) A, C, G, H, I, J, K, L and M, the streptococcal superantigen (SSA) and the streptococcal mitogenic exotoxin Z (SmeZ) [15].…”

Section: Introductionmentioning

confidence: 99%

Streptococcus pyogenes bacteraemia, emm types and superantigen profiles

Rantala

Vähäkuopus

Siljander

et al. 2011

Eur J Clin Microbiol Infect Dis

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The aim of this study was to investigate the emm types and superantigen profiles of bacteraemic group A streptococcal (GAS; Streptococcus pyogenes) isolates and to detect possible associations between the molecular characteristics of isolates and the clinical presentations of disease. In this population-based study, 87 bacteraemic GAS isolates from adult patients in Pirkanmaa Health District (HD), Finland, during the period 1995-2004 were emm typed and genotyped for superantigen (SAg) profiles. The epidemiological and clinical data of the patients were analysed with the microbiological characterisation data. Among the 87 isolates, 18 different emm types were found. emm1, emm28 and emm81 were the three most common types, covering 52% of isolates. The prevalence of specific emm types showed high variability during the 10-year study period. We could not find any association between the emm type and clinical features of bacteraemic infection, such as underlying diseases, disease manifestations or case fatality. Of nine superantigen genes examined, speA and speC were identified in 20 and 30% of the strains, respectively. No association was found between disease manifestation and the presence of single superantigen genes. The 26-valent GAS vaccine would have covered only 62% of isolates causing invasive disease in Pirkanmaa HD during the study period.

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Superantigen Genes Are More Important than theemmType for the Invasiveness of Group AStreptococcusInfection

Cited by 46 publications

References 54 publications

Invasive infections due to Streptococcus pyogenes: seasonal variation of severity and clinical characteristics, Iceland, 1975 to 2012

Invasive infections due to Streptococcus pyogenes: seasonal variation of severity and clinical characteristics, Iceland, 1975 to 2012

Naturally occurring single amino acid replacements in a regulatory protein alter streptococcal gene expression and virulence in mice

Streptococcus pyogenes bacteraemia, emm types and superantigen profiles

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