An rhs gene of Pseudomonas aeruginosa encodes a virulence protein that activates the inflammasome
An rhs gene of Pseudomonas aeruginosa encodes a virulence protein that activates the inflammasome
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DOI：
10.1073/pnas.1109285109
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发表时间：
2012-01-24
影响因子：
11.1
通讯作者：
Hauser, Alan R.
中科院分区：
文献类型：
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作者：
Kung, Vanderlene L.;Khare, Sonal;Hauser, Alan R.
rhs基因是一个神秘的复合基因家族，广泛存在于革兰氏阴性菌中。在这项研究中，我们表征了rhsT，一个铜绿假单胞菌的rhs基因，编码一种有毒蛋白。rhsT与吞噬细胞接触后被诱导表达。RhsT蛋白暴露于细菌表面，转运进入吞噬细胞；这些细胞随后经历了炎症小体介导的死亡。此外，RhsT以炎症小体依赖的方式增强宿主强效促炎细胞因子IL-1 β和IL-18的分泌。在小鼠急性肺炎模型中，感染缺乏rhsT的铜绿假单胞菌菌株与IL-18产生减少、募集白细胞减少、肺部细菌负荷减少和动物存活率提高相关。因此，rhsT编码了激活炎性小体的毒力决定因子。
The rhs genes are a family of enigmatic composite genes, widespread among Gram-negative bacteria. In this study, we characterized rhsT, a Pseudomonas aeruginosa rhs gene that encodes a toxic protein. Expression of rhsT was induced upon contact with phagocytic cells. The RhsT protein was exposed on the bacterial surface and translocated into phagocytic cells; these cells subsequently underwent inflammasome-mediated death. Moreover, RhsT enhanced host secretion of the potent proinflammatory cytokines IL-1 beta and IL-18 in an inflammasome-dependent manner. In a mouse model of acute pneumonia, infection with a P. aeruginosa strain lacking rhsT was associated with less IL-18 production, fewer recruited leukocytes, reduced pulmonary bacterial load, and enhanced animal survival. Thus, rhsT encodes a virulence determinant that activates the inflammasome.