SpvC is a Salmonella effector with phosphothreonine lyase activity on host mitogen-activated protein kinases
Author(s)
Type
Journal Article
Abstract
SpvC is encoded by the Salmonella virulence plasmid. We have investigated the biochemical function of SpvC and the mechanism by which it is secreted by bacteria and translocated into infected macrophages. We constructed a strain carrying a deletion in spvC and showed that the strain is attenuated for systemic virulence in mice. SpvC can be secreted in vitro by either the SPI-1 or SPI-2 type III secretion systems. Cell biological and genetic experiments showed that translocation of the protein into the cytosol of macrophages by intracellular bacteria is dependent on the SPI-2 T3SS. Using antibodies specific to phospho-amino acids and mass spectrometry we demonstrate that SpvC has phosphothreonine lyase activity on full-length phospho-Erk (pErk) and a synthetic 13-amino-acid phospho-peptide containing the TXY motif. A Salmonella strain expressing spvC from a plasmid downregulated cytokine release from infected cells.
Date Issued
2008-02-15
Date Acceptance
2008-01-17
Citation
Molecular Microbiology, 2008, 67 (6), pp.1371-1383
ISSN
1365-2958
Publisher
Wiley
Start Page
1371
End Page
1383
Journal / Book Title
Molecular Microbiology
Volume
67
Issue
6
Copyright Statement
© 2008 The Authors. Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
Sponsor
Medical Research Council (MRC)
Grant Number
G0800148
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Microbiology
BIOCHEMISTRY & MOLECULAR BIOLOGY
MICROBIOLOGY
III SECRETION SYSTEM
TYPHIMURIUM VIRULENCE PLASMID
MONOCYTE-DERIVED MACROPHAGES
INTRACELLULAR SALTS MEDIUM
GENE-EXPRESSION
ANTIBIOTIC-RESISTANCE
CHROMOSOMAL GENES
ESCHERICHIA-COLI
ENTERICA
CELLS
Amino Acid Motifs
Animals
Carbon-Oxygen Lyases
Cells, Cultured
Cytokines
Enzyme-Linked Immunosorbent Assay
Extracellular Signal-Regulated MAP Kinases
Female
HeLa Cells
Humans
JNK Mitogen-Activated Protein Kinases
Macrophages
Mice
Mice, Inbred BALB C
Mitogen-Activated Protein Kinases
Phosphorylation
Phosphothreonine
Salmonella Infections
Salmonella typhimurium
Spectrometry, Mass, Electrospray Ionization
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Virulence
p38 Mitogen-Activated Protein Kinases
Hela Cells
06 Biological Sciences
11 Medical And Health Sciences
07 Agricultural And Veterinary Sciences
Publication Status
Published