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

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. The group B streptococcal type VII secretion system (T7SS) comprises four subtypes, which encode similar machinery but unique effectors, including putative LXG toxins. We show that subtypes I and II are prevalent among GBS clinical isolates and hypothesize that T7SS subtype‐specific effectors may impact GBS female genital tract colonization.