Extensive Diversity of Streptococcus pyogenes in a Remote Human Population Reflects Global-Scale Transmission Rather than Localised Diversification

Rebecca J Towers,Bart J Currie,Jonathan R Carapetis,Gordon Dougan,Mark J Walker,Mark R Davies,Philip M Giffard,Igor Mokrousov

doi:10.1371/journal.pone.0073851

Abstract

The Indigenous population of the Northern Territory of Australia (NT) suffers from a very high burden of Streptococcus pyogenes disease, including cardiac and renal sequelae. The aim of this study was to determine if S. pyogenes isolated from this population represent NT endemic strains, or conversely reflect strains with global distribution. emm sequence typing data were used to select 460 S. pyogenes isolates representing NT S. pyogenes diversity from 1987–2008. These isolates were genotyped using either multilocus sequence typing (MLST) or a high resolution melting-based MLST surrogate (Minim typing). These data were combined with MLST data from other studies on NT S. pyogenes to yield a set of 731 MLST or Minim typed isolates for analysis. goeBURST analysis of MLST allelic profiles and neighbour-joining trees of the MLST allele sequences revealed that a large proportion of the known global S. pyogenes MLST-defined diversity has now been found in the NT. Specifically, fully sequence typed NT isolates encompass 19% of known S. pyogenes STs and 43% of known S. pyogenes MLST alleles. These analyses provided no evidence for major NT-endemic strains, with many STs and MLST alleles shared between the NT and the rest of the world. The relationship between the number of known Minim types, and the probability that a Minim type identified in a calendar year would be novel was determined. This revealed that Minim types typically persist in the NT for >1 year, and indicate that the majority of NT Minim types have been identified. This study revealed that many diverse S. pyogenes strains exhibit global scale mobility that extends to isolated populations. The burden of S. pyogenes disease in the NT is unlikely to be due to the nature of NT S. pyogenes strains, but is rather a function of social and living conditions.

Highlights

The bacterium Streptococcus pyogenes is an important human pathogen [1]
Where new MelTs, or new combinations of emmST and MelT were observed, multilocus sequence typing (MLST) was performed. These data were combined with MLST data previously reported [17,18], and MLST data extracted from 70 genome sequences currently under analysis, the final result being 731 Northern Territory of Australia (NT) isolates with associated Minim and/or MLST data. (Table S2)
We have shown that S. pyogenes isolated from the sparse and often isolated human population of the NT represents a remarkably large subset of the known global S. pyogenes population structure and diversity, as defined by MLST

Summary

Introduction

The bacterium Streptococcus pyogenes is an important human pathogen [1]. It is a common cause of pharyngitis (‘‘strep throat’’) and skin infections. It can cause invasive and systemic infections that may be life threatening A distinctive aspect of S. pyogenes infections is the rare but significant occurrence of immune related sequelae. [4,5] ARF and RHD are largely regarded as sequels of pharyngitis, and APSGN as a sequel of skin infection. ARF, RHD and APSGN are all rare in developed countries and are associated with high burdens of infection, and sub-optimal provision of health care [1]

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Conclusion