LysR-type transcriptional regulator OvrB encoded in O island 9 drives enterohemorrhagic Escherichia coli O157:H7 virulence

Virulence. 2019 Dec;10(1):783-792. doi: 10.1080/21505594.2019.1661721.

Abstract

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 (O157) is a major foodborne pathogen that causes severe illness in humans worldwide. The genome of O157 contains 177 genomic islands known as O islands (OIs), including Shiga toxin-converting phages (OI-45 and OI-93) and the locus for enterocyte effacement (LEE) pathogenicity island (OI-148). However, most genes in OIs are uncharacterized and code for unknown functions. In this study, we demonstrated, for the first time, that OI-9 encodes a novel transcriptional activator, Z0346 (named OvrB), which is required for bacterial adherence to host cells and LEE gene expression in O157. OvrB directly binds to the promoter region of LEE1 and activates the transcription of ler (encoding a master regulator of LEE genes), which in turn activates LEE1-5 genes to promote O157 adherence. Furthermore, mouse oral infection assays showed that OvrB promotes O157 colonization in the mouse intestine. Finally, OvrB is shown to be a widespread transcriptional activator of virulence genes in other enterohemorrhagic and enteropathogenic Escherichia coli serotypes. Our work significantly expands the understanding of bacterial virulence control and provides new evidence suggesting that horizontally transferred regulator genes mediate LEE gene expression.

Keywords: Enterohemorrhagic; Genomic island; O islands; O157:H7; Shiga toxin (Stx); locus of enterocyte effacement (LEE).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Adhesion
  • Escherichia coli Infections / microbiology
  • Escherichia coli O157 / genetics*
  • Escherichia coli O157 / pathogenicity*
  • Escherichia coli Proteins / genetics*
  • Female
  • Gastrointestinal Tract / microbiology
  • Gene Expression Regulation, Bacterial / genetics*
  • Genomic Islands*
  • Mice
  • Mice, Inbred BALB C
  • Mutation
  • Trans-Activators / genetics*
  • Transcription Factors / genetics*
  • Virulence / genetics
  • Virulence Factors / genetics

Substances

  • Escherichia coli Proteins
  • LrhA protein, E coli
  • OvrB protein, E coli
  • Trans-Activators
  • Transcription Factors
  • Virulence Factors

Grants and funding

This work was supported by the National Science Foundation of China [31800125]; National Science Foundation of China [31530083]; Natural Science Foundation of Tianjin [17JCQNJC09300].