MrvR, a Group B Streptococcus Transcription Factor that Controls Multiple Virulence Traits

摘要: Abstract Streptococcus agalactiae (group B Streptococcus; GBS) remains a dominant cause of serious neonatal infections. One aspect GBS that renders it particularly virulent during the perinatal period is its ability to invade chorioamniotic membranes and persist in amniotic fluid, which nutritionally deplete rich fetal immunologic factors such as antimicrobial peptides. We used next-generation sequencing transposon-genome junctions (Tn-seq) identify five genes promote survival presence human fluid. confirmed our Tn-seq findings using novel CRISPR inhibition (CRISPRi) gene expression knockdown system. This analysis showed one gene, encodes GntR-class transcription factor we named MrvR, conferred significant fitness benefit generated an isogenic targeted knockout mrvR found have growth defect fluid relative wild type parent strain. In addition growing poorly also biofilm vitro. Subsequent vivo studies that, while was able persistent murine vaginal colonization, pregnant mice colonized with strain did not develop preterm labor despite consistent invasion uterus fetoplacental units. contrast, consistently deliver prematurely. Similarly, sepsis model 87% infected died within three days, none died. order better understand mechanism by this newly identified controls virulence, performed electrophoresis mobility shift assays recombinant MrvR whole-genome transcriptomic on strains. show binds own promoter region, suggesting likely self-regulation. RNA-seq revealed affects wide range across chromosome. Nucleotide biosynthesis salvage pathways were highly represented among set differentially expressed genes, linkage between purine or pyrimidine availability activity multiple virulence traits.