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

Area of Science:

• Microbiology
• Genetics
• Infectious Diseases

Background:

• Group A Streptococcus (GAS; Streptococcus pyogenes) serotype M28 isolates are linked to puerperal sepsis.
• The RD2 pathogenicity island in M28 GAS enhances female reproductive tract colonization.
• The role of RD2 in other GAS serotypes remains largely unexplored.

Purpose of the Study:

• To investigate the functional consequences of introducing the RD2 pathogenicity island into non-M28 GAS serotypes (M1, M49, M59).
• To assess how RD2 acquisition impacts GAS colonization, survival in human blood, and adherence to vaginal epithelial cells.
• To elucidate the molecular mechanisms underlying serotype-specific phenotypic variations following RD2 acquisition.

Main Methods:

• Gain-of-function study involving the introduction of the RD2 island into serotype M1, M49, and M59 GAS isolates.
• Mouse vaginal colonization model to evaluate colonization efficiency (percentage and CFU levels).
• In vitro assays for survival in heparinized whole human blood and adherence to human vaginal epithelial cell lines.
• Transcriptomic analysis to compare gene expression profiles between RD2-containing and parental GAS isolates.

Main Results:

• All RD2-containing GAS derivatives exhibited enhanced colonization in the mouse vaginal model compared to parental strains.
• Phenotypic differences were observed in bacterial survival and adherence, demonstrating serotype-specific effects of RD2 acquisition.
• Transcriptomic data revealed that RD2 alters core genome gene expression in a serotype-dependent manner.

Conclusions:

• The RD2 pathogenicity island promotes GAS colonization across different serotypes.
• The phenotypic impact of RD2 acquisition is modulated by the specific GAS serotype, contributing to its variable distribution.
• Understanding these serotype-specific interactions is crucial for explaining the prevalence and pathogenicity of GAS.