A Comparison of Group A Streptococci from Invasive and Uncomplicated Infections: Are Virulent Clones Responsible for Serious Streptococcal Infections?

Abstract

From the mid-1980s, numerous reports of invasive group A streptococcal infections suggested that "highly virulent clones" were responsible. However, there have been virtually no extensive reports and comparisons of diverse temporal and geographic community isolates from uncomplicated throat infections to confirm the hypothesis. A unique collection of such "control" strains allowed in-depth assessment of association of M serotypes 1, 3, and 28 "clones" with invasive infections. Clones were defined by using small-fragment chromosomal restriction-enzyme analysis, pulsed-field gel electrophoresis, and M protein gene (emm) sequencing. After comparison with controls, no clone within these M serotypes had statistically increased association with invasive infections. The prevalence of specific virulence-associated clones appeared to essentially reflect their normal population prevalence. Although this does exclude other potential streptococcal factors, these findings suggest that host factors including individual and population-based immunity must also be significant in influencing infection potential.

Susceptibility to severe streptococcal sepsis: use of a large set of isogenic mouse lines to study genetic and environmental factors

“…3,[34][35][36][37] For example, we have previously demonstrated a dominant effect of HLA class II allelic polymorphisms in severe GAS sepsis. 9,10 We also provided biological confirmation of these HLA associations in vitro 10,38,39 and in vivo.…”

The M protein of group A Streptococcus is a key virulence factor and a clinically relevant strain identification marker

“…4,15,16,19 As more individuals are exposed to a specific serotype, that serotype becomes less fit due to the inability to transmit successfully between the decreased numbers of remaining susceptible individuals, a phenomenon known as herd immunity. [20][21][22][23] As herd immunity to a specific serotype increases, other serotypes become favored through a relative increase in transmission and hence reproduction. Because this process generally favors unique (new or recently rare) serological variants, evolutionary pressure is thought to drive the process of diversification in primary antigens and to drive cyclical turnovers in the dominance of existing serotypes.…”

Rise and Persistence of Global M1T1 Clone ofStreptococcus pyogenes

“…Although many GAS serotypes are capable of causing severe diseases, a few were more frequently isolated from patients with severe cases, e.g., M1, M3, M18, and M28 strains ( Table 2 in online Technical Appendix). However, whether those serotypes cause more severe disease because of their hypervirulence or because they were also the most prevalently isolated strains in the community at that time was not clear (11,12). These possibilities are not mutually exclusive, but in fact may be related.…”