A Mobile Genetic Element Promotes the Association Between Serotype M28 Group A Streptococcus Isolates and Cases of Puerperal Sepsis

Abstract

Background Bacterial infections following childbirth—so-called puerperal infections—cause morbidity in 5%–10% of all new mothers. At low frequency, the infection can spread to the blood, resulting in life-threatening sepsis known as puerperal sepsis. Pathogens causing puerperal sepsis include group A Streptococcus (GAS), and epidemiological analyses have identified isolates of a single serotype, M28, as being nonrandomly associated with cases of puerperal sepsis. The genomes of serotype M28 GAS isolates harbor a 36.3-kb mobile genetic element of apparent group B Streptococcus origin, termed region of difference 2 (RD2). Methods The phenotypic (determined via tissue culture and a vaginal colonization model) and regulatory (determined via RNA sequencing analysis) contributions of RD2 were assessed by comparing parental, RD2 deletion mutant, and complemented mutant serotype M28 GAS strains. Results RD2 affords serotype M28 isolates an enhanced ability to adhere to human vaginal epithelial cells and to colonize the female reproductive tract in a mouse model of infection. In addition, RD2 influences the abundance of messenger RNAs from >100 core chromosomal GAS genes. Conclusions The data are consistent with RD2 directly, via encoded virulence factors, and indirectly, via encoded regulatory proteins, modifying the virulence potential of GAS and contributing to the decades-old association of serotype M28 isolates with cases of puerperal sepsis.

The group A Streptococcus accessory protein RocA: regulatory activity, interacting partners and influence on disease potential

“…The many diseases caused by GAS differ dramatically in their clinical presentation and lethality. Additional layers of variability are observed due to strain‐ and serotype‐specific differences in the ability of isolates to cause distinct diseases, with molecular mechanisms such as the modulation of regulatory systems, or gene gain/loss, accounting for such variation (Cao et al , ; Sarkar and Sumby, ; Jain et al , ; Kachroo et al , ). At the center of strain‐ and serotype‐specific variability in GAS disease potential is the CovR/S two‐component system.…”

Genome-Wide Screens Identify Group A Streptococcus Surface Proteins Promoting Female Genital Tract Colonization and Virulence

“…A recent study reported that deletion of the entire RD2 region conferred decreased ability of an M28 GAS strain to adhere in vitro to immortalized human vaginal epithelial cells and to colonize the female genital tract in a mouse model of infection. 70 Our screen did not identify genes in the RD2 region as contributing factors for GAS colonization in this NHP female genital tract infection model. At least three possibilities may explain this observation.…”

Streptococcus pyogenes infects human endometrium by limiting its immune response

“…They also express one collagen-binding protein, Epf, in addition to the shared pilus and SpyAD (40). Finally, RD2, a 32 kb DNA region quasi specific to emm28 strains modify, via encoded virulence factors and regulators, the virulence potential of emm28 strains, contributing to their association with puerperal fever (41). The composition of the decidua surface and all these factors may explain the capacity of GAS to adhere to this tissue, a critical step in invasive puerperal fever.…”