Genome-Wide fitness analysis of group B Streptococcus in human amniotic fluid reveals a transcription factor that controls multiple virulence traits

• DOI: 10.1371/journal.ppat.1009116
• Publication Date: 2021-03-08T18:34:22Z
• Authors: Allison N. Dammann; Anna B. Chamby; Andrew J. Catomeris; Kyle M. Davidson; Hervé Tettelin; Jan-Peter van Pij...; Kathyayini P. Gop...; Mary F. Keith; Jordan L. Elder; Adam J. Ratner; Thomas A. Hooven
• Keywords: 0301 basic medicine; Virulence; QH301-705.5; Gene Expression Regulation, Bacterial; RC581-607; Amniotic Fluid; Streptococcus agalactiae; 3. Good health; Mice; 03 medical and health sciences; Phenotype; Bacterial Proteins; Streptococcal Infections; Animals; Humans; Immunologic diseases. Allergy; Biology (General); Research Article; Transcription Factors

Streptococcus agalactiae (group B ; 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 deletion mrvR had growth defect fluid relative wild type parent strain. The strain also biofilm vitro . Subsequent vivo studies while mutant was able persistent murine vaginal colonization, pregnant mice colonized with did not develop preterm labor despite consistent invasion uterus fetoplacental units. In contrast, consistently deliver prematurely. sepsis model significantly decreased lethality. order better understand mechanism by this newly identified controls virulence, performed RNA-seq on strains, revealed affects wide range across chromosome. Nucleotide biosynthesis salvage pathways were highly represented among set differentially expressed genes, suggesting MrvR may be involved regulating nucleotide availability.