Heterogeneity of the Group B Streptococcal Type VII Secretion System and Influence on Colonization of the Female Genital Tract

Authors

Brady L Spencer
Alyx M Job
Clare M Robertson
Zainab A Hameed
Camille Serchejian
Caitlin S Wiafe-Kwakye
Jéssica C Mendonça
Morgan A Apolonio
Prescilla E Nagao
Melody N Neely
Natalia Korotkova
Konstantin V Korotkov
Kathryn A Patras
Kelly S Doran

Publication Date

8-1-2023

Journal

Molecular Microbiology

DOI

10.1111/mmi.15115

PMID

37357823

PMCID

PMC10527989

PubMedCentral® Posted Date

8-1-2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Infant, Newborn, Female, Humans, Bacterial Proteins, Type VII Secretion Systems, Virulence, Operon, Genitalia, Female, Streptococcal Infections, Streptococcus agalactiae, Vagina, Streptococcus agalactiae, group B Streptococcus, GBS, Type VII Secretion System, genetic diversity, colonization, operon, effectors

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.