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The Salmonella virulence protein SifA is a G protein antagonist

Laurie K Jackson1, Parwez Nawabi, Cristiana Hentea

  • 1Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.

Proceedings of the National Academy of Sciences of the United States of America
|September 13, 2008
PubMed

Insights

Salmonella virulence protein SifA antagonizes host protein Rab9 by binding to SKIP, disrupting host cell processes crucial for bacterial infection. This mimicry mechanism highlights a novel bacterial strategy for disease.

Area of Science:

  • Microbiology
  • Cell Biology
  • Molecular Biology

Background:

  • Salmonella virulence protein SifA is essential for intracellular proliferation.
  • SifA interacts with host protein SKIP, influencing the Salmonella-containing vacuole (SCV) and Salmonella-induced filaments (Sifs).
  • SifA possesses a conserved WxxxE motif, suggesting potential G protein mimicry.

Purpose of the Study:

  • To investigate the interaction between SifA, SKIP, and the host GTPase Rab9.
  • To elucidate the mechanism of SifA's function and potential G protein mimicry.
  • To understand how SifA manipulates host cell processes for Salmonella survival.

Main Methods:

  • Co-immunoprecipitation assays to study protein interactions.
  • GTP-binding assays to assess Rab9:SKIP interaction dependency.
  • Cellular knockdown studies to evaluate the roles of SKIP and Rab9.
  • Microscopy to observe the localization of LAMP1 and the SCV.

Main Results:

  • SifA binds to SKIP, inhibiting the interaction between SKIP and the GTPase Rab9.
  • SifA binding to SKIP is stronger than Rab9:SKIP binding.
  • Knockdown of SKIP or Rab9 affects lysosome associated membrane protein 1 (LAMP1) distribution.
  • SifA utilizes its WxxxE motif to bind SKIP, suggesting G protein antagonism.
  • Rab9 can reverse SifA-mediated effects on LAMP1 recruitment and SCV localization.

Conclusions:

  • Salmonella SifA acts as an antagonist of the host GTPase Rab9 by binding to SKIP.
  • Bacterial G protein mimicry, exemplified by SifA, can involve antagonism of host GTPases.
  • This mechanism allows Salmonella to manipulate host cell membranes and vacuole dynamics for intracellular survival.

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