The RD2 Pathogenicity Island Modifies the Disease Potential of the Group A Streptococcus

Serotype M28 isolates of the group A Streptococcus (GAS; Streptococcus pyogenes) are nonrandomly associated with cases of puerperal sepsis, a potentially life-threatening infection that can occur in women following childbirth. Previously, we discovered that the 36.3-kb RD2 pathogenicity island, which is present in serotype M28 isolates but lacking from most other isolates, promotes the ability of M28 GAS to colonize the female reproductive tract. Here, we performed a gain-of-function study in which we introduced RD2 into representative serotype M1, M49, and M59 isolates and assessed the phenotypic consequences of RD2 acquisition. All RD2-containing derivatives colonized a higher percentage of mice, and at higher CFU levels, than did the parental isolates in a mouse vaginal colonization model. However, for two additional phenotypes, survival in heparinized whole human blood and adherence to two human vaginal epithelial cell lines, there were serotype-specific differences from RD2 acquisition. Using transcriptomic comparisons, we identified that such differences may be a consequence of RD2 altering the abundance of transcripts from select core genome genes along serotype-specific lines. Our study is the first that interrogates RD2 function in GAS serotypes other than M28 isolates, shedding light on variability in the phenotypic consequences of RD2 acquisition and informing on why this mobile genetic element is not ubiquitous in the GAS population.

Automated summary

The study found that serotype M28 isolates of group A Streptococcus (GAS) enhance their colonization ability in the female reproductive tract through the RD2 pathogenicity island, and introducing RD2 into other serotypes also increases colonization rates in mice. However, the impact of RD2 on survival and adherence to human vaginal epithelial cells varies depending on the serotype.