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
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
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DOI：
10.1111/j.1365-2958.2011.07637.x
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发表时间：
2011-06
影响因子：
3.6
通讯作者：
T. Miki;K. Akiba;M. Iguchi;H. Danbara;N. Okada
中科院分区：
文献类型：
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作者：
T. Miki;K. Akiba;M. Iguchi;H. Danbara;N. Okada
由色杆菌致病岛1和1a（Cpi-1/-1a）编码的III型分泌系统（T3 SS）对于紫色色杆菌的发病机理至关重要。T3 SS依赖性毒力通常以III型效应毒力功能为特征，但Cpi-1/-1a T3 SS效应蛋白的全部谱尚不清楚。在这项研究中，我们发现Cpi-1/-1a T3 SS的表达受主调节因子CilA控制。我们使用DNA微阵列的转录谱来定义CilA调节子，并鉴定编码T3 SS效应子的基因，其易位到宿主细胞中依赖于Cpi-1/-1a T3 SS。从这些效应物中，我们发现科普（CV 0296）在其C末端部分与Rho GTP酶的鸟嘌呤核苷酸交换因子（GEF）具有相似性。科普的N-末端部分（1-81个氨基酸）和作为推定伴侣的CivB是其易位所需的。科普特异性激活Rac 1和Cdc 42，随后诱导肌动蛋白细胞骨架重排。有趣的是，C。violaceum以Cpi-1/-1a-编码的T3 SS-和科普-依赖性方式侵入人类上皮HeLa细胞。最后，C.在小鼠中，缺乏科普并表达GEF活性缺陷的CopE-G168 V的violaceum菌株的毒力减弱，表明科普有助于该病原体的毒力。
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.