Chromobacterium pathogenicity island 1 type III secretion system is a major virulence determinant for Chromobacterium violaceum-induced cell death in hepatocytes.
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.
Miki
Tsuyoshi
T
Department of Microbiology, School of Pharmacy, Kitasato University, Minato-ku, Tokyo 108-8641, Japan.
Iguchi
Mirei
M
Department of Microbiology, School of Pharmacy, Kitasato University, Minato-ku, Tokyo 108-8641, Japan.
Akiba
Kinari
K
Department of Microbiology, School of Pharmacy, Kitasato University, Minato-ku, Tokyo 108-8641, Japan.
Hosono
Masato
M
Department of Microbiology, School of Pharmacy, Kitasato University, Minato-ku, Tokyo 108-8641, Japan.
Sobue
Tomoyoshi
T
Department of Microbiology, School of Pharmacy, Kitasato University, Minato-ku, Tokyo 108-8641, Japan.
Danbara
Hirofumi
H
Department of Microbiology, School of Pharmacy, Kitasato University, Minato-ku, Tokyo 108-8641, Japan.
Okada
Nobuhiko
N
Department of Microbiology, School of Pharmacy, Kitasato University, Minato-ku, Tokyo 108-8641, Japan.
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*
D058947:Bacterial Secretion Systems; D037521:Virulence Factors