Heterogeneity of the group B streptococcal type VII secretion system and influence on colonization of the female genital tract

Mol Microbiol. 2023 Aug;120(2):258-275. doi: 10.1111/mmi.15115. Epub 2023 Jun 26.

Abstract

Type VIIb secretion systems (T7SSb) in Gram-positive bacteria facilitate physiology, interbacterial competition, and/or virulence via EssC ATPase-driven secretion of small ɑ-helical proteins and toxins. Recently, we characterized T7SSb in group B Streptococcus (GBS), a leading cause of infection in newborns and immunocompromised adults. GBS T7SS comprises four subtypes based on variation in the C-terminus of EssC and the repertoire of downstream effectors; however, the intraspecies diversity of GBS T7SS and impact on GBS-host interactions remains unknown. Bioinformatic analysis indicates that GBS T7SS loci encode subtype-specific putative effectors, which have low interspecies and inter-subtype homology but contain similar domains/motifs and therefore may serve similar functions. We further identify orphaned GBS WXG100 proteins. Functionally, we show that GBS T7SS subtype I and III strains secrete EsxA in vitro and that in subtype I strain CJB111, esxA1 appears to be differentially transcribed from the T7SS operon. Furthermore, we observe subtype-specific effects of GBS T7SS on host colonization, as CJB111 subtype I but not CNCTC 10/84 subtype III T7SS promotes GBS vaginal colonization. Finally, we observe that T7SS subtypes I and II are the predominant subtypes in clinical GBS isolates. This study highlights the potential impact of T7SS heterogeneity on host-GBS interactions.

Keywords: Streptococcus agalactiae; GBS; colonization; effectors; genetic diversity; group B Streptococcus; operon; type VII secretion system.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Female
  • Genitalia, Female / metabolism
  • Humans
  • Infant, Newborn
  • Operon / genetics
  • Streptococcal Infections* / microbiology
  • Streptococcus agalactiae / genetics
  • Streptococcus agalactiae / metabolism
  • Type VII Secretion Systems* / genetics
  • Vagina / metabolism
  • Vagina / microbiology
  • Virulence

Substances

  • Bacterial Proteins
  • Type VII Secretion Systems