cas9 Enhances Bacterial Virulence by Repressing the regR Transcriptional Regulator in Streptococcus agalactiae

Infect Immun. 2018 Feb 20;86(3):e00552-17. doi: 10.1128/IAI.00552-17. Print 2018 Mar.

Abstract

Clustered regularly interspaced palindromic repeats (CRISPR) and their associated cas genes have been demonstrated to regulate self-genes and virulence in many pathogens. In this study, we found that inactivation of cas9 caused reduced adhesion and intracellular survival of the piscine Streptococcus agalactiae strain GD201008-001 and significantly decreased the virulence of this strain in zebrafish and mice. Further investigation indicated that the regR transcriptional regulator was upregulated in the Δcas9 mutant. As regR mediates the repression of hyaluronidase, a critical factor involved in opening the blood-brain barrier (BBB) in mice, cas9-mediated repression of regR transcription is important for S. agalactiae to open the BBB and thereby cause meningitis in animals. This study expands our understanding of endogenous gene regulation mediated by CRISPR-Cas systems in bacteria.

Keywords: Streptococcus agalactiae; bacterial virulence; cas9; hyaluronidase; regR transcriptional regulator.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Blood-Brain Barrier / microbiology
  • CRISPR-Cas Systems
  • Endonucleases / genetics
  • Endonucleases / metabolism*
  • Female
  • Gene Expression Regulation, Bacterial
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Streptococcal Infections / microbiology*
  • Streptococcus agalactiae / enzymology*
  • Streptococcus agalactiae / genetics
  • Streptococcus agalactiae / pathogenicity*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic*
  • Virulence
  • Zebrafish

Substances

  • Bacterial Proteins
  • RegR protein, bacteria
  • Transcription Factors
  • Endonucleases