Identification of a conserved bacterial protein secretion system in Vibrio cholerae using the Dictyostelium host model system
Identification of a conserved bacterial protein secretion system in Vibrio cholerae using the Dictyostelium host model system
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DOI：
10.1073/pnas.0510322103
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发表时间：
2006-01-31
影响因子：
11.1
通讯作者：
Mekalanos, JJ
中科院分区：
文献类型：
--
作者：
Pukatzki, S;Ma, AT;Mekalanos, JJ
霍乱弧菌与环境中的其他人类病原体一样，能够在单细胞真核生物的捕食下幸存下来。 O1 和 O139 血清群菌株引起霍乱，而非 O1/非 O139 菌株通过不明确的机制引起人类感染。使用盘基网柄菌作为模型宿主，我们鉴定了非 O1/非 O139 霍乱弧菌菌株的毒力机制，该机制涉及缺乏 N 末端疏水前导序列的蛋白质的细胞外易位。因此，我们将这些基因命名为毒力相关分泌的“VAS”基因，并且我们提出这些基因编码原型“VI型”分泌系统。我们表明，霍乱弧菌细胞通过接触依赖性机制对阿米巴盘基网柄菌和哺乳动物 J774 巨噬细胞产生细胞毒性，需要 vas 基因。大量革兰氏阴性细菌病原体携带与 vas 基因同源的基因和该途径分泌的潜在效应蛋白（即溶血素共调节蛋白和 VgrG）。据报道，其他细菌物种的血管同系物突变会减弱动物和培养巨噬细胞的毒力。因此，编码 VAS 相关 VI 型分泌系统的基因可能在微生物发病机制中发挥重要的保守功能，并代表疫苗和抗菌药物治疗的另一类靶标。
The bacterium Vibrio cholerae, like other human pathogens that reside in environmental reservoirs, survives predation by unicellular eukaryotes. Strains of the O1 and O139 serogroups cause cholera, whereas non-O1/non-O139 strains cause human infections through poorly defined mechanisms. Using Dictyostelium discoideum as a model host, we have identified a virulence mechanism in a non-O1/non-O139 V. cholerae strain that involves extracellular translocation of proteins that lack N-terminal hydrophobic leader sequences. Accordingly, we have named these genes "VAS" genes for virulence-associated secretion, and we propose that these genes encode a prototypic "type VI" secretion system. We show that vas genes are required for cytotoxicity of V. cholerae cells toward Dictyostelium amoebae and mammalian J774 macrophages by a contact-dependent mechanism. A large number of Gram-negative bacterial pathogens carry genes homologous to vas genes and potential effector proteins secreted by this pathway (i.e., hemolysin-coregulated protein and VgrG). Mutations in vas homologs in other bacterial species have been reported to attenuate virulence in animals and cultured macrophages. Thus, the genes encoding the VAS-related, type VI secretion system likely play an important conserved function in microbial pathogenesis and represent an additional class of targets for vaccine and antimicrobial drug-based therapies.