title: Chromobacterium pathogenicity island 1 type III secretion system is a major virulence determinant for Chromobacterium violaceum-induced cell death in hepatocytes.
abstract: Chromobacterium violaceum is a Gram-negative bacterium that causes fatal septicaemia in humans and animals. C. violaceum ATCC 12472 possesses genes associated with two distinct type III secretion systems (T3SSs). One of these systems is encoded by Chromobacterium pathogenicity islands 1 and 1a (Cpi-1/-1a), another is encoded by Chromobacterium pathogenicity island 2 (Cpi-2). Here we show that C. violaceum causes fulminant hepatitis in a mouse infection model, and Cpi-1/-1a-encoded T3SS is required for its virulence. In addition, using C. violaceum strains with defined mutations in the genes that encode the Cpi-1/-1a or Cpi-2 locus in combination with cultured mammalian cell lines, we found that C. violaceum is able to induce cytotoxicity in a Cpi-1/-1a-dependent manner. Characterization of Chromobacterium-induced cytotoxicity revealed that cell lysis by C. violaceum infection involves the formation of pore structures on the host cell membrane, as demonstrated by protection by cytotoxicity in the presence of osmoprotectants. Finally, we demonstrated that CipB, a Cpi-1/-1a effector, is implicated in translocator-mediated pore formation and the ability of CipB to form a pore is essential for Chromobacterium-induced cytotoxicity. These results strongly suggest that Cpi-1/-1a-encoded T3SS is a virulence determinant that causes fatal infection by the induction of cell death in hepatocytes.
authors.affiliation: Department of Microbiology, School of Pharmacy, Kitasato University, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Miki
authors.affiliation: Department of Microbiology, School of Pharmacy, Kitasato University, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Mirei
authors.initials: M
authors.lastname: Iguchi
authors.affiliation: Department of Microbiology, School of Pharmacy, Kitasato University, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Kinari
authors.initials: K
authors.lastname: Akiba
authors.affiliation: Department of Microbiology, School of Pharmacy, Kitasato University, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Hosono
authors.affiliation: Department of Microbiology, School of Pharmacy, Kitasato University, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Sobue
authors.affiliation: Department of Microbiology, School of Pharmacy, Kitasato University, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Danbara
authors.affiliation: Department of Microbiology, School of Pharmacy, Kitasato University, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Okada
mesh_terms: D000818:Animals; D058947:Bacterial Secretion Systems; D012634:Bodily Secretions; D016923:Cell Death; D002861:Chromobacterium / Q000235:genetics* / Q000254:growth & development* / Q000472:pathogenicity; D004195:Disease Models, Animal; D044404:Genomic Islands; D016905:Gram-Negative Bacterial Infections / Q000382:microbiology / Q000473:pathology; D006520:Hepatitis, Animal / Q000382:microbiology / Q000473:pathology; D022781:Hepatocytes / Q000382:microbiology / Q000502:physiology; D051379:Mice; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D058947:Bacterial Secretion Systems; D037521:Virulence Factors