Chromobacterium pathogenicity island 1 type III secretion system is a major virulence determinant for Chromobacterium violaceum‐induced cell death in hepatocytes

Abstract

SummaryChromobacterium 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.

Sequential Mycoplasma pneumoniae pneumonia and Chromobacterium violaceum skin abscess in a pediatric patient

“…It is a free-living organism, ubiquitously and saprophytically inhabiting in the soil and water in tropical and sub-tropical regions. Isolates from natural habitats are capable of adapting and surviving in diverse adverse environments and ecosystems [8][9][10][11]. Chromobacterium violaceum was first described as a potential pathogen in water buffalos in the Philippines by Wooley in 1905 and in humans in Malaysia by Lesslar in 1927 [10,12].…”

“…Chromobacterium violaceum was first described as a potential pathogen in water buffalos in the Philippines by Wooley in 1905 and in humans in Malaysia by Lesslar in 1927 [10,12]. Several cases of Chromobacterium violaceum human infections have since been reported despite of the bacterium being considered as of low infectivity and usually not as a human pathogen [9,10]. The type III secretory system (TTSS) components of Chromobacterium violaceum encoded by open reading frames (ORFs), as revealed by complete genome sequencing, allow secretions of effector molecules into the host cells leading to cytoskeletal rearrangement, and have been found to differ from those TTSS in other gram-negative pathogenic bacteria.…”

“…The type III secretory system (TTSS) components of Chromobacterium violaceum encoded by open reading frames (ORFs), as revealed by complete genome sequencing, allow secretions of effector molecules into the host cells leading to cytoskeletal rearrangement, and have been found to differ from those TTSS in other gram-negative pathogenic bacteria. The lack of ORFs responsible for invasions such as invI and invH, and the secretion of tyrosin phosphatase SptP in Chromobacterium violaceum may explain its opportunistic pathogenicity [9,13].…”

Global Transcriptional Response to Organic Hydroperoxide and the Role of OhrR in the Control of Virulence Traits in Chromobacterium violaceum

“…Clinical manifestations include abscess formation in the skin, liver, and lung and, in many cases, progression to death (19,25). A type III secretion system (T3SS) is essential for C. violaceum virulence in mice (26,27), and the T3SS needle protein CprI can be recognized by the NLRC4 inflammasome in human macrophages (28). The clearance of C. violaceum infection is mediated by the NLRC4 inflammasome that triggers pyroptosis in macrophages or natural killer cytotoxicity in liver cells to expose C. violaceum to neutrophil killing (29).…”

Membrane and Chaperone Recognition by the Major Translocator Protein PopB of the Type III Secretion System of Pseudomonas aeruginosa

“…Because the internal diameter of the needle is on the order of 25 Å, it is believed that effectors must travel in a semi-unfolded state (2, 3) due to energy provided by an ATPase located at the base of the system (4 -6). Introduction of point mutations into key proteins of the T3SS have shown to be highly deleterious for the cytotoxicity potential of certain pathogens (7)(8)(9)(10)(11), and T3SS-deficient strains display attenuated infectivity in animal models (12)(13)(14), indicating that an understanding of T3SS formation and regulation mechanisms could lead to the development of strategies for infection control.…”