Invasion genes are not required for Salmonella enterica serovar typhimurium to breach the intestinal epithelium: Evidence that Salmonella pathogenicity island 1 has alternative functions during infection

Salmonella enterica serovar Typhimurium invasion genes are necessary for ba cterial invasion of intestinal epithelial cells and are thought to allow sa lmonellae to enter and cross the intestinal epithelium during infection. Ma ny invasion genes are encoded on Salmonella pathogenicity island 1 (SPI1), and their expression is activated by HilA, a transcription factor also enco ded on SPI1. We have studied the role of Salmonella invasion genes during i nfection of mice following intragastric inoculation. We have found that str ains containing a mutation in hilA or invG were recovered from the intestin al contents, intestinal tissues, and systemic tissues at a lower frequency than their parental wild-type strain. In contrast, a strain in which SPI1 i s deleted was recovered from infected mice at a frequency similar to that o f its parental wild-type strain. The Delta SPI1 phenotype indicates that S. enterica does not require invasion genes to cross the intestinal epitheliu m and infect systemic tissues. This result has forced us to reconsider the long-held belief that invasion genes directly mediate bacterial infection o f the intestinal mucosa and traversion of the intestinal barrier during inf ection. Instead, our results suggest that hilA is required for bacterial co lonization of the host intestine. The seemingly contradictory phenotype of the Delta SPI1 mutant suggests that deletion of another gene(s) encoded on SPI1 suppresses the hilA mutant defect. We propose a model for S. enterica pathogenesis in which hilA and invasion genes are required for salmonellae to overcome a host clearance response elicited by another SPI1 gene product (s).