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 intra-species 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 inter-species 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. Further, we observe subtype-specific effects of GBS T7SS on host colonization, as subtype I but not subtype III T7SS promotes GBS vaginal persistence. 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 novel variant of theListeria monocytogenestype VII secretion system EssC component is associated with an Rhs toxin

“…We also show that a small subset of essC1 , essC2 and essC3 genomes encode a truncated EssC of a different variant, along with the likely substrate protein/s recognised by that specific EssC type. Four variants of EssC have previously been reported in S. aureus (55), and recently it was shown that there are four EssC types in group B Streptococcus (56), suggesting that heterogeneity is a general feature of the T7SSb.…”

A novel variant of the Listeria monocytogenes type VII secretion system EssC component is associated with an Rhs toxin

“…We also show that a small subset of essC1 , essC2 and essC3 genomes encode a truncated EssC of a different variant, along with the likely substrate protein(s) recognized by that specific EssC type. Four variants of EssC have previously been reported in Staphylococcus aureus [58], and recently it was shown that there are four EssC types in group B Streptococcus [59], suggesting that heterogeneity is a general feature of the T7SSb.…”

Interbacterial competition mediated by the type VIIb secretion system

“…esxA is typically encoded upstream of the other T7SSb components and is in some cases transcribed separately from the rest of the locus, as seen in group B Streptococcus (GBS) and some strains of S. aureus. In other strains of S. 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][34][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] (Fig. 3).…”

“…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.…”