The Campylobacter jejuni CiaD effector co-opts the host cell protein IQGAP1 to promote cell entry

Nat Commun. 2021 Feb 26;12(1):1339. doi: 10.1038/s41467-021-21579-5.

Abstract

Campylobacter jejuni is a foodborne pathogen that binds to and invades the epithelial cells lining the human intestinal tract. Maximal invasion of host cells by C. jejuni requires cell binding as well as delivery of the Cia proteins (Campylobacter invasion antigens) to the host cell cytosol via the flagellum. Here, we show that CiaD binds to the host cell protein IQGAP1 (a Ras GTPase-activating-like protein), thus displacing RacGAP1 from the IQGAP1 complex. This, in turn, leads to the unconstrained activity of the small GTPase Rac1, which is known to have roles in actin reorganization and internalization of C. jejuni. Our results represent the identification of a host cell protein targeted by a flagellar secreted effector protein and demonstrate that C. jejuni-stimulated Rac signaling is dependent on IQGAP1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bacterial Proteins / metabolism
  • Campylobacter Infections / metabolism
  • Campylobacter jejuni / metabolism*
  • Campylobacter jejuni / pathogenicity
  • Cell Line
  • Epithelial Cells / metabolism*
  • Epithelial Cells / microbiology*
  • Flagella / metabolism
  • Gene Knockdown Techniques
  • Host-Pathogen Interactions / physiology
  • Humans
  • Signal Transduction
  • Transcriptome
  • ras GTPase-Activating Proteins / genetics
  • ras GTPase-Activating Proteins / metabolism*

Substances

  • Bacterial Proteins
  • IQ motif containing GTPase activating protein 1
  • ras GTPase-Activating Proteins