Chromobacterium pathogenicity island 1 type III secretion system is a major virulence determinant for Chromobacterium violaceum‐induced cell death in hepatocytes
Chromobacterium pathogenicity island 1 type III secretion system is a major virulence determinant for Chromobacterium violaceum‐induced cell death in hepatocytes
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DOI：
10.1111/j.1365-2958.2010.07248.x
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发表时间：
2010-08
影响因子：
3.6
通讯作者：
T. Miki;M. Iguchi;K. Akiba;M. Hosono;Tomoyoshi Sobue;H. Danbara;N. Okada
中科院分区：
文献类型：
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作者：
T. Miki;M. Iguchi;K. Akiba;M. Hosono;Tomoyoshi Sobue;H. Danbara;N. Okada
紫色色杆菌是一种革兰氏阴性细菌，可导致人类和动物致命性败血症。C.紫罗兰ATCC 12472具有与两种不同的III型分泌系统（T3 SS）相关的基因。其中一个系统由色杆菌致病岛1和1a（Cpi-1/-1a）编码，另一个系统由色杆菌致病岛2（Cpi-2）编码。在这里，我们展示了C。violaceum在小鼠感染模型中引起暴发性肝炎，其毒力需要Cpi-1/-1a-编码的T3 SS。此外，利用C.在与培养的哺乳动物细胞系组合的编码Cpi-1/-1a或Cpi-2基因座的基因中具有确定突变的C. violaceum能够以Cpi-1/-1a-依赖性方式诱导细胞毒性。对色杆菌诱导的细胞毒性的表征显示，C.如通过在存在细胞毒性保护剂的情况下的细胞毒性保护所证明的，紫孢菌感染涉及在宿主细胞膜上形成孔结构。最后，我们证明了CipB（一种Cpi-1/-1a效应物）与转运蛋白介导的孔形成有关，CipB形成孔的能力对于色杆菌诱导的细胞毒性至关重要。这些结果强烈表明，Cpi-1/-1a-编码的T3 SS是一种毒力决定因子，通过诱导肝细胞中的细胞死亡引起致死性感染。
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.