Peptide-assisted degradation of the Salmonella MgtC virulence factor

EMBO J. 2008 Feb 6;27(3):546-57. doi: 10.1038/sj.emboj.7601983. Epub 2008 Jan 17.

Abstract

MgtC is a virulence factor common to several intracellular pathogens that is required for intramacrophage survival and growth in magnesium-depleted medium. In Salmonella enterica, MgtC is coexpressed with the MgtB magnesium transporter and transcription of the mgtCB operon is induced by magnesium deprivation. Despite the high level of mgtCB transcriptional induction in magnesium-depleted medium, the MgtC protein is hardly detected in a wild-type Salmonella strain. Here, we show that downregulation of MgtC expression is dependent on a hydrophobic peptide, MgtR, which is encoded by the mgtCB operon. Our results suggest that MgtR promotes MgtC degradation by the FtsH protease, providing a negative regulatory feedback. Bacterial two-hybrid assays demonstrate that MgtR interacts with the inner-membrane MgtC protein. We identified mutant derivatives of MgtR and MgtC that prevent both regulation and interaction between the two partners. In macrophages, overexpression of the MgtR peptide led to a decrease of the replication rate of Salmonella. This study highlights the role of peptides in bacterial regulatory mechanisms and provides a natural antagonist of the MgtC virulence factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Amino Acid Sequence
  • Animals
  • Bacterial Proteins / biosynthesis
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Base Sequence
  • Cation Transport Proteins / biosynthesis
  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / metabolism*
  • Cell Line
  • Down-Regulation / physiology
  • Gene Expression Regulation, Bacterial / physiology
  • Macrophages / microbiology
  • Mice
  • Molecular Sequence Data
  • Peptides / physiology*
  • Regulatory Sequences, Nucleic Acid / physiology
  • Salmonella typhimurium / metabolism*
  • Salmonella typhimurium / pathogenicity
  • Virulence / physiology
  • Virulence Factors / metabolism*

Substances

  • Bacterial Proteins
  • Cation Transport Proteins
  • Peptides
  • Virulence Factors
  • Adenosine Triphosphatases
  • MgtB protein, Salmonella typhimurium
  • MgtC protein, Salmonella typhimurium

Associated data

  • GENBANK/EU154350