A novel PhoP-regulated locus encoding the cytolysin ClyA and the secreted invasin TaiA of Salmonella enterica serovar Typhi is involved in virulence
A novel PhoP-regulated locus encoding the cytolysin ClyA and the secreted invasin TaiA of Salmonella enterica serovar Typhi is involved in virulence
复制标题
DOI：
10.1099/mic.0.022988-0
复制
发表时间：
2009-02-01
期刊：
影响因子：
2.8
通讯作者：
Daigle, France
中科院分区：
文献类型：
--
作者：
Faucher, Sebastien P.;Forest, Chantal;Daigle, France
伤寒沙门氏菌引起一种称为伤寒的人类限制性全身感染。我们已经确定了一个伤寒基因组区域编码两个ORF，STY 1498和STY 1499，这是在感染人类巨噬细胞和组织在一个操纵子。STY 1498对应于clyA，其编码孔形成溶细胞素，STY 1499编码27 kDa的蛋白质，没有任何归因的功能，我们将其命名为TaiA（Typhi-associated invasin A）。为了评估这些基因在伤寒发病机制中的作用，构建了含有clyA或taiA非极性突变的同基因伤寒菌株。在巨噬细胞中，taiA参与增加吞噬作用，因为taiA缺失减少了细菌摄取，而clyA减少或控制了细菌生长，因为clyA缺失增强了巨噬细胞内伤寒杆菌的存活而不影响细胞毒性。在上皮细胞中，taiA的缺失对侵袭没有影响，而clyA的缺失增强了伤寒杆菌的侵袭率，并降低了细胞毒性。taiA在伤寒杆菌或大肠杆菌中的过表达导致上皮细胞的更高侵袭率。我们已经证明TaiA的分泌独立于沙门氏菌致病岛（SPI）-1和SPI-2三型分泌系统。我们已经表明，这个操纵子是由与毒性相关的调节PhoP。此外，我们的研究结果表明，该操纵子的产物可能参与促进巨噬细胞作为伤寒的庇护水库的使用，并允许在宿主体内长期存在。
Salmonella enterica serovar Typhi causes a human-restricted systemic infection called typhoid fever. We have identified a Typhi genomic region encoding two ORFs, STY1498 and STY1499, that are expressed during infection of human macrophages and organized in an operon. STY1498 corresponds to clyA, which encodes a pore-forming cytolysin, and STY1499 encodes a 27 kDa protein, without any attributed function, which we have named TaiA (Typhi-associated invasin A). In order to evaluate the roles of these genes in Typhi pathogenesis, isogenic Typhi strains harbouring a non-polar mutation of either clyA or taiA were constructed. In macrophages, taiA was involved in increasing phagocytosis, as taiA deletion reduced bacterial uptake, whereas clyA reduced or controlled bacterial growth, as clyA deletion enhanced Typhi survival within macrophages without affecting cytotoxicity. In epithelial cells, deletion of taiA had no effect on invasion, whereas deletion of clyA enhanced the Typhi invasion rate, and reduced cytotoxicity. Overexpression of taiA in Typhi or in Escherichia coli resulted in a higher invasion rate of epithelial cells. We have demonstrated that TaiA is secreted independently of both the Salmonella pathogenicity island (SPI)-1 and the SPI-2 type three secretion systems. We have shown that this operon is regulated by the virulence-associated regulator PhoP. Moreover, our results revealed that products of this operon might be involved in promoting the use of macrophages as a sheltered reservoir for Typhi and allowing long-term persistence inside the host.