Elucidation of a complete mechanical signaling and virulence activation pathway in enterohemorrhagic Escherichia coli

Cell Rep. 2022 Apr 5;39(1):110614. doi: 10.1016/j.celrep.2022.110614.

Abstract

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is an important extracellular human pathogen. The initial adherence of EHEC to host cells is a major cue for transcriptional induction of the locus of enterocyte effacement (LEE) genes to promote colonization and pathogenesis, but the mechanism through which this adherence is sensed and the LEE is induced remains largely elusive. Here, we report a complete signal transduction pathway for this virulence activation process. In this pathway, the outer-membrane lipoprotein NlpE senses a mechanical cue generated from initial host adherence and activates the BaeSR two-component regulatory system; the response regulator BaeR then directly activates the expression of airA located on O-island-134 and encoding a LEE transcriptional activator. Disruption of this pathway severely attenuates EHEC O157:H7 virulence both in vitro and in vivo. This study provides further insights into the evolution of EHEC pathogenesis and the host-pathogen interaction.

Keywords: AirA; BaeSR TCS; CP: Microbiology; EHEC; LEE pathogenicity island; Ler; NlpE; initial adherence; virulence activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Adhesion
  • Bacterial Outer Membrane Proteins / metabolism
  • Enterohemorrhagic Escherichia coli* / genetics
  • Escherichia coli Infections*
  • Escherichia coli O157* / genetics
  • Escherichia coli O157* / metabolism
  • Escherichia coli Proteins* / genetics
  • Escherichia coli Proteins* / metabolism
  • Gene Expression Regulation, Bacterial
  • Humans
  • Lipoproteins / genetics
  • Lipoproteins / metabolism
  • Phosphoproteins / metabolism
  • Virulence / genetics

Substances

  • Bacterial Outer Membrane Proteins
  • Escherichia coli Proteins
  • Lipoproteins
  • NlpE protein, E coli
  • Phosphoproteins