1887

Abstract

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 , 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 or were constructed. In macrophages, was involved in increasing phagocytosis, as deletion reduced bacterial uptake, whereas reduced or controlled bacterial growth, as deletion enhanced Typhi survival within macrophages without affecting cytotoxicity. In epithelial cells, deletion of had no effect on invasion, whereas deletion of enhanced the Typhi invasion rate, and reduced cytotoxicity. Overexpression of in Typhi or in resulted in a higher invasion rate of epithelial cells. We have demonstrated that TaiA is secreted independently of both the 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.

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2009-02-01
2020-01-18
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