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首页> 外文期刊>Infection and immunity >Activities of Pseudomonas aeruginosa Effectors Secreted by the Type III Secretion System In Vitro and during Infection
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Activities of Pseudomonas aeruginosa Effectors Secreted by the Type III Secretion System In Vitro and during Infection

机译：III型分泌系统在体外和感染过程中分泌的铜绿假单胞菌效应子的活性

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Pseudomonas aeruginosa utilizes a number of distinct pathways to secrete proteins that play various roles during infection. These include the type II secretion system, which is responsible for the secretion of the majority of exoproducts into the surrounding environment, including toxins and degradative enzymes. In contrast, the type III secretion system mediates the delivery of protein effectors directly into the cytoplasm of the host cell. Using tissue culture assays and a mouse acute-pneumonia model, we have determined the contribution of each of the type III effectors during infection. In strain PAK, ExoS is the major cytotoxin required for colonization and dissemination during infection. ExoT confers protection of tissue culture cells from type III-dependent lysis, while ExoY seemed to have little effect on cytotoxicity. ExoU is over 100-fold more cytotoxic than ExoS. The cytotoxicity of type II secretion was determined following deletion of the genes for the more toxic type III secretion system. The participation of these secretion systems during lifelong colonization of cystic fibrosis (CF) patients is unclear. By comparing clonal strains from the same patient isolated at the initial onset of P. aeruginosa infection and more than a decade later, after chronic colonization has been established, we show that initial strains are more cytotoxic than chronic strains that have evolved to reduce type III secretion. Constitutive expression of genes for the type III secretion system restored ExoS secretion but did not always reestablish cytotoxicity, suggesting that CF strains accumulate a number of mutations to reduce bacterial toxicity to the host.
机译：铜绿假单胞菌利用许多不同的途径分泌在感染过程中发挥多种作用的蛋白质。其中包括II型分泌系统，该系统负责将大多数外生产物分泌到周围环境中，包括毒素和降解酶。相反，III型分泌系统介导蛋白质效应子直接传递到宿主细胞的细胞质中。使用组织培养测定法和小鼠急性肺炎模型，我们确定了感染期间每种III型效应子的作用。在PAK菌株中，ExoS是感染期间定植和传播所需的主要细胞毒素。 ExoT赋予组织培养细胞免受III型依赖的裂解的保护，而ExoY似乎对细胞毒性几乎没有影响。 ExoU的细胞毒性比ExoS高100倍以上。在删除毒性更大的III型分泌系统的基因后，确定II型分泌的细胞毒性。这些分泌系统在囊性纤维化（CF）患者终生定植期间是否参与尚不清楚。通过比较来自 P初次发作的同一患者的克隆菌株。铜绿假单胞菌感染以及十多年后的慢性定殖建立之后，我们证明初始菌株比已经进化为减少III型分泌的慢性菌株更具细胞毒性。 III型分泌系统基因的组成型表达恢复了ExoS分泌，但并不总是重建细胞毒性，这表明CF菌株积累了许多突变，以减少对宿主的细菌毒性。

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