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.
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.
authors: Department of Microbiology, School of Pharmacy, Kitasato University, Minato-ku, Tokyo 108-8641, Japan.
authors: Tsuyoshi
authors: T
authors: Miki
authors: Kinari
authors: K
authors: Akiba
authors: Mirei
authors: M
authors: Iguchi
authors: Hirofumi
authors: H
authors: Danbara
authors: Nobuhiko
authors: N
authors: Okada
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002861:Chromobacterium / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D004847:Epithelial Cells / Q000382:microbiology*; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D044404:Genomic Islands; D016905:Gram-Negative Bacterial Infections / Q000382:microbiology*; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D020662:Guanine Nucleotide Exchange Factors