Salmonella typhi encodes a functional cytolethal distending toxin that is delivered into host cells by a bacterial-internalization pathway
Salmonella typhi encodes a functional cytolethal distending toxin that is delivered into host cells by a bacterial-internalization pathway
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DOI：
10.1073/pnas.0400932101
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发表时间：
2004-03-30
影响因子：
11.1
通讯作者：
Galán, JE
中科院分区：
文献类型：
--
作者：
Haghjoo, E;Galán, JE
许多细菌病原体编码细胞致死膨胀毒素（CDT），它通过造成DNA损伤导致宿主细胞在细胞周期中停滞。CDT由CdtA、CdtB和CdtC三种蛋白质组成。CdtB是具有酶活性的A亚基，具有类似dna酶i的活性，而CdtA和CdtC则是介导CdtB进入宿主细胞的异聚B亚基。我们在这里表明，沙门氏菌伤寒血清型编码CDT活性，这取决于CdtB同源蛋白的功能。值得注意的是，伤寒沙门氏菌血清型不编码CdtA或CdtC的明显同源物。相反，我们发现毒性以及cdtB的表达需要细菌内化到宿主细胞中。我们提出了一种毒素传递途径，其中细菌内化减轻了对CDT毒素B亚基功能等效物的需求。
Many bacterial pathogens encode the cytolethal distending toxin (CDT), which causes host cells to arrest during their cell cycle by inflicting DNA damage. CDT is composed of three proteins, CdtA, CdtB, and CdtC. CdtB is the enzymatically active or A subunit, which possesses DNase I-like activity, whereas CdtA and CdtC function as heteromeric B subunits that mediate the delivery of CdtB into host cells. We show here that Salmonella enterica serovar Typhi encodes CDT activity, which depends on the function of a CdtB homologous protein. Remarkably, S. enterica serovar Typhi does not encode apparent homologs of CdtA or CdtC. Instead, we found that toxicity, as well as cdtB expression, requires bacterial internalization into host cells. We propose a pathway of toxin delivery in which bacterial internalization relieves the requirement for the functional equivalent of the B subunit of the CDT toxin.