The Multivalent Adhesion Molecule SSO1327 plays a key role in Shigella sonnei pathogenesis

Mol Microbiol. 2016 Feb;99(4):658-73. doi: 10.1111/mmi.13255. Epub 2015 Nov 17.

Abstract

Shigella sonnei is a bacterial pathogen and causative agent of bacillary dysentery. It deploys a type III secretion system to inject effector proteins into host epithelial cells and macrophages, an essential step for tissue invasion and immune evasion. Although the arsenal of bacterial effectors and their cellular targets have been studied extensively, little is known about the prerequisites for deployment of type III secreted proteins during infection. Here, we describe a novel S. sonnei adhesin, SSO1327 which is a multivalent adhesion molecule (MAM) required for invasion of epithelial cells and macrophages and for infection in vivo. The S. sonnei MAM mediates intimate attachment to host cells, which is required for efficient translocation of type III effectors into host cells. SSO1327 is non-redundant to IcsA; its activity is independent of type III secretion. In contrast to the up-regulation of IcsA-dependent and independent attachment and invasion by deoxycholate in Shigella flexneri, deoxycholate negatively regulates IcsA and MAM in S. sonnei resulting in reduction in attachment and invasion and virulence attenuation in vivo. A strain deficient for SSO1327 is avirulent in vivo, but still elicits a host immune response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesins, Bacterial / genetics
  • Adhesins, Bacterial / isolation & purification
  • Adhesins, Bacterial / metabolism*
  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / isolation & purification
  • Bacterial Proteins / metabolism*
  • DNA-Binding Proteins / genetics
  • Deoxycholic Acid / metabolism
  • Disease Models, Animal
  • Dysentery, Bacillary / microbiology*
  • Dysentery, Bacillary / physiopathology
  • Epithelial Cells / microbiology
  • Guinea Pigs
  • HeLa Cells
  • Humans
  • Keratoconjunctivitis / microbiology
  • Larva / microbiology
  • Macrophages / microbiology
  • Moths
  • Shigella flexneri / metabolism
  • Shigella sonnei / genetics*
  • Shigella sonnei / pathogenicity*
  • Transcription Factors / genetics
  • Type III Secretion Systems / genetics
  • Type III Secretion Systems / metabolism
  • Up-Regulation
  • Virulence

Substances

  • Adhesins, Bacterial
  • Bacterial Proteins
  • DNA-Binding Proteins
  • Transcription Factors
  • Type III Secretion Systems
  • virG protein, Shigella flexneri
  • Deoxycholic Acid