Abstract

BackgroundThe M type-specific surface protein antigens encoded by the 5' end of emm genes are targets of protective host immunity and attractive vaccine candidates against infection by Streptococcus pyogenes, a global human pathogen. A history of genetic change in emm was evaluated for a worldwide collection of > 500 S. pyogenes isolates that were defined for genetic background by multilocus sequence typing of housekeeping genes.ResultsOrganisms were categorized by genotypes that roughly correspond to throat specialists, skin specialists, and generalists often recovered from infections at either tissue site. Recovery of distant clones sharing the same emm type was ~4-fold higher for skin specialists and generalists, as compared to throat specialists. Importantly, emm type was often a poor marker for clone. Recovery of clones that underwent recombinational replacement with a new emm type was most evident for the throat and skin specialists. The average ratio of nonsynonymous substitutions per nonsynonymous site (Ka) and synonymous substitutions per synonymous site (Ks) was 4.9, 1.5 and 1.3 for emm types of the throat specialist, skin specialist and generalist groups, respectively.ConclusionData indicate that the relationships between emm type and genetic background differ among the three host tissue-related groups, and that the selection pressures acting on emm appear to be strongest for the throat specialists. Since positive selection is likely due in part to a protective host immune response, the findings may have important implications for vaccine design and vaccination strategies.

Highlights

  • The M type-specific surface protein antigens encoded by the 5' end of emm genes are targets of protective host immunity and attractive vaccine candidates against infection by Streptococcus pyogenes, a global human pathogen

  • multilocus sequence typing (MLST) and emm typing data was previously reported for 493 of the isolates under study [23,32,33]; an additional 89 isolates were included based on their large geographic distance relative to isolates sharing that emm type; emm alleles were determined for the majority of isolates

  • The recovery of all 3 genotypes involved in the horizontal gene transfer (HGT) event – donor, recipient, and new clone – from the extant S. pyogenes population was evaluated, based on the findings presented in Tables 3 and 4

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Summary

Introduction

The M type-specific surface protein antigens encoded by the 5' end of emm genes are targets of protective host immunity and attractive vaccine candidates against infection by Streptococcus pyogenes, a global human pathogen. A molecular arms race between pathogen and host often emerges when an immune response favors the selection of microorganisms displaying altered antigens on their surface. Genetic change provides the raw material upon which natural selection acts, and a host immune response is one of the strongest selection pressures a microbial pathogen will encounter. The fibrillar M protein molecule present on the surface of Streptococcus pyogenes, a bacterial pathogen afflicting humans throughout the world, is often the target of a protective immune response mounted during infection [1,2,3]. Strong protective immunity to S. pyogenes infection is often M type-specific

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