The Salmonella effector protein SifA plays a dual role in virulence

Sci Rep. 2015 Aug 13;5:12979. doi: 10.1038/srep12979.

Abstract

The virulence of Salmonella relies on the expression of effector proteins that the bacterium injects inside infected cells. Salmonella enters eukaryotic cells and resides in a vacuolar compartment on which a number of effector proteins such as SifA are found. SifA plays an essential role in Salmonella virulence. It is made of two distinct domains. The N-terminal domain of SifA interacts with the host protein SKIP. This interaction regulates vacuolar membrane dynamics. The C-terminal has a fold similar to other bacterial effector domains having a guanine nucleotide exchange factor activity. Although SifA interacts with RhoA, it does not stimulate the dissociation of GDP and the activation of this GTPase. Hence it remains unknown whether the C-terminal domain contributes to the function of SifA in virulence. We used a model of SKIP knockout mice to show that this protein mediates the host susceptibility to salmonellosis and to establish that SifA also contributes to Salmonella virulence independently of its interaction with SKIP. We establish that the C-terminal domain of SifA mediates this SKIP-independent contribution. Moreover, we show that the two domains of SifA are functionally linked and participate to the same signalling cascade that supports Salmonella virulence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics*
  • GTP Phosphohydrolases / chemistry
  • GTP Phosphohydrolases / metabolism
  • Gene Expression Regulation, Bacterial
  • Glycoproteins / chemistry
  • Glycoproteins / genetics*
  • Guanosine Diphosphate / metabolism
  • HeLa Cells
  • Humans
  • Mice
  • Mice, Knockout
  • Microtubules / chemistry
  • Microtubules / metabolism
  • Phosphoric Monoester Hydrolases / genetics*
  • Phosphoric Monoester Hydrolases / metabolism
  • Protein Folding
  • Protein Structure, Tertiary
  • Salmonella / chemistry
  • Salmonella / metabolism*
  • Salmonella / pathogenicity
  • rho GTP-Binding Proteins / chemistry
  • rho GTP-Binding Proteins / metabolism

Substances

  • Bacterial Proteins
  • Glycoproteins
  • SifA protein, Salmonella
  • Guanosine Diphosphate
  • Pps protein, mouse
  • Phosphoric Monoester Hydrolases
  • GTP Phosphohydrolases
  • RhoA protein, mouse
  • rho GTP-Binding Proteins