Invasion Genes Are Not Required forSalmonella entericaSerovar Typhimurium To Breach the Intestinal Epithelium: Evidence ThatSalmonellaPathogenicity Island 1 Has Alternative Functions during Infection

Abstract

Salmonella entericaserovar Typhimurium invasion genes are necessary for bacterial invasion of intestinal epithelial cells and are thought to allow salmonellae to enter and cross the intestinal epithelium during infection. Many invasion genes are encoded onSalmonellapathogenicity island 1 (SPI1), and their expression is activated by HilA, a transcription factor also encoded on SPI1. We have studied the role ofSalmonellainvasion genes during infection of mice following intragastric inoculation. We have found that strains containing a mutation inhilAorinvGwere recovered from the intestinal contents, intestinal tissues, and systemic tissues at a lower frequency than their parental wild-type strain. In contrast, a strain in which SPI1 is deleted was recovered from infected mice at a frequency similar to that of its parental wild-type strain. The ΔSPI1 phenotype indicates thatS. entericadoes not require invasion genes to cross the intestinal epithelium and infect systemic tissues. This result has forced us to reconsider the long-held belief that invasion genes directly mediate bacterial infection of the intestinal mucosa and traversion of the intestinal barrier during infection. Instead, our results suggest thathilAis required for bacterial colonization of the host intestine. The seemingly contradictory phenotype of the ΔSPI1 mutant suggests that deletion of another gene(s) encoded on SPI1 suppresses thehilAmutant defect. We propose a model forS. entericapathogenesis in whichhilAand invasion genes are required for salmonellae to overcome a host clearance response elicited by another SPI1 gene product(s).