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.
摘要:
革兰氏阳性细菌中的VIIb型分泌系统(T7SSb)促进生理,细菌间竞争,和/或通过EssCATPase驱动分泌的小α螺旋蛋白和毒素产生毒力。最近,我们在B组链球菌(GBS)中表征了T7SSb,新生儿和免疫功能低下的成年人感染的主要原因。GBST7SS包含基于EssCC末端变异和下游效应子集合的四种亚型;然而,GBST7SS的种内多样性以及对GBS-宿主相互作用的影响尚不清楚.生物信息学分析表明,GBST7SS基因座编码亚型特异性推定效应子,它们具有低的种间和亚型间同源性,但包含相似的结构域/基序,因此可能具有相似的功能。我们进一步鉴定了孤立的GBSWXG100蛋白。功能上,我们显示GBST7SSI和III亚型菌株在体外分泌EsxA,而在I亚型菌株CJB111中,esxA1似乎从T7SS操纵子转录。此外,我们观察到GBST7SS对宿主定植的亚型特异性作用,由于CJB111I型而非CNCTC10/84III型T7SS促进GBS阴道定植。最后,我们观察到T7SS亚型I和II是临床GBS分离株中的主要亚型.这项研究强调了T7SS异质性对宿主-GBS相互作用的潜在影响。