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

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.

A high throughput assay provides novel insight into type VII secretion inStaphylococcus aureus

“…4A). Recent analysis of other T7SSb LXG toxins has revealed a common mechanistic feature for secretion, involving formation of a hetero-oligomeric pre-secretion complex between the LXG domain and helical hairpin partner proteins encoded at the same genetic locus as the toxin [24, 26, 27, 37]. Logically, the TspA LXG domain should also be expected to require similar helical binding partners to generate a secretion-competent structure.…”

An in-depth analysis and exploreation with focus on the biofilm inStaphylococcus aureus

“…The copyright holder for this preprint this version posted May 6, 2024. ; https://doi.org/10.1101/2024.05.05.592613 doi: bioRxiv preprint invasion of host cells and disrupt their normal functions, thus augmenting the survival and proliferation of pathogen (34). Furthermore, T7SS aids bacteria in resource competition against other microbes (35). The secreted proteins by T7SS can directly or indirectly curtail the growth of competitors, enhancing bacterial competitiveness and survival.…”

Interbacterial competition mediated by the type VIIb secretion system

“…aureus as well as S. gallolyticus , esxA is co-transcribed with the rest of the T7SS structural genes, although RNAseq data show that S. aureus esxA transcript levels are much greater than for other T7SS genes [15, 33–35]. Some species carry two copies of esxA , the significance of which is not yet known [16, 36].…”

“…Although their genetic arrangement can vary, the genes encoding the core T7SSb components are well conserved and are usually encoded at the 5′ end of T7SSb loci. By contrast, the 3′ ends of T7SSb loci exhibit a high level of genetic diversity, both between and within species [15, 20, 35] (). This variable downstream region encodes strain-specific substrates, accessory secretion factors, immunity genes and proteins with as yet unidentified functions.…”

“…In a murine model of L. monocytogenes infection, colonisation of the spleen and liver were unexpectedly impaired by T7SS-dependent secretion of EsxA [ 62 ]. Furthermore, a study using a murine model of female genital tract colonisation to compare T7SSb subtypes across different strains of GBS ( Streptococcus agalactiae ) found the T7-dependence of host colonisation to vary across strains [ 35 ]. Taken together these data suggest that the strain-specific T7 substrate repertoire may determine host phenotypes in colonisation and virulence studies.…”