RRC ID 35365
Author Miki T, Akiba K, Iguchi M, Danbara H, Okada N.
Title The Chromobacterium violaceum type III effector CopE, a guanine nucleotide exchange factor for Rac1 and Cdc42, is involved in bacterial invasion of epithelial cells and pathogenesis.
Journal Mol Microbiol
Abstract The type III secretion system (T3SS) encoded by Chromobacterium pathogenicity islands 1 and 1a (Cpi-1/-1a) is critical for Chromobacterium violaceum pathogenesis. T3SS-dependent virulence is commonly characterized by type III effector virulence function, but the full repertoire of the effector proteins of Cpi-1/-1a T3SS is unknown. In this study, we showed that expression of Cpi-1/-1a T3SS is controlled by the master regulator CilA. We used transcriptional profiling with DNA microarrays to define CilA regulon and identified genes encoding T3SS effectors whose translocation into host cells was dependent on Cpi-1/-1a T3SS. From these effectors, we found that CopE (CV0296) has similarities to a guanine nucleotide exchange factor (GEF) for Rho GTPases in its C-terminal portion. The N-terminal portions (1-81 amino acids) of CopE and a CivB as a putative chaperone were required for its translocation. CopE specifically activates Rac1 and Cdc42 followed by the induction of actin cytoskeletal rearrangement. Interestingly, C. violaceum invades human epithelial HeLa cells in a Cpi-1/-1a-encoded T3SS- and CopE-dependent manner. Finally, C. violaceum strains lacking copE and expressing a CopE-G168V deficient in GEF activity were attenuated for virulence in mice, suggesting that CopE contributes to the virulence of this pathogen.
Volume 80(5)
Pages 1186-203
Published 2011-6-1
DOI 10.1111/j.1365-2958.2011.07637.x
PMID 21435035
MeSH Amino Acid Motifs Animals Bacterial Proteins / chemistry Bacterial Proteins / genetics Bacterial Proteins / metabolism* Cell Line Chromobacterium / chemistry Chromobacterium / genetics Chromobacterium / metabolism* Chromobacterium / pathogenicity* Epithelial Cells / microbiology* Female Gene Expression Regulation, Bacterial Genomic Islands Gram-Negative Bacterial Infections / microbiology* Guanine Nucleotide Exchange Factors / chemistry Guanine Nucleotide Exchange Factors / genetics Guanine Nucleotide Exchange Factors / metabolism* Humans Mice Mice, Inbred C57BL Virulence
IF 3.418
Times Cited 15
Prokaryotes E. coli pJB861