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

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.

Whole genome sequencing reveals extensive community-level transmission of group AStreptococcusin remote communities

“…Previous studies in this regional endemic setting have demonstrated a considerable diversity of GAS when longitudinal sampling was performed in a small number of communities [26,27], or with broader sampling for diversity across the entire region [28]. There was considerable diversity of GAS clones as represented by nine STs in 11 households, and also a lack of variation within each ST, indicating very recent transmission of each of the STs.…”

Acute rheumatic fever and rheumatic heart disease

“…Given the ongoing high rates of ARF and RHD in developing countries, any selective pressure on host susceptibility caused by premature mortality seems not to have had a substantial effect in these places. However, it is quite possible that selective pressures on organism factors in developing countries might be affected by those in industrialized nations, given emerging evidence of mobility of GAS strains on a global scale 53 .…”

Group A Streptococcal Carriage and Seroepidemiology in Children up to 10 Years of Age in Australia

“…burden of serious complications or sequelae is concentrated in children in developing countries and in indigenous children in developed countries. [7][8][9][10][11][12] Development of a broadly effective GAS vaccine has been challenging. There is considerable strain diversity within and between countries, and the epidemiology of GAS is dynamic, with shifts in serotype prevalence within populations.…”

“…There is considerable strain diversity within and between countries, and the epidemiology of GAS is dynamic, with shifts in serotype prevalence within populations. 11,13,14 The GAS M protein is a major virulence factor and target for vaccine development. 15,16 However, the diversity of M types in circulation around the world makes this vaccine approach difficult to enable sufficient coverage.…”