Systemic and enteric colonization of pigs by a hilA signature-tagged mutant of Salmonella choleraesuis

Although host adapted to pigs, Salmonella enterica serovar Choleraesuis (S. choleraesuis) can induce a virulent foodborne salmonellosis in humans. To directly investigate virulence factors of S. choleraesuis, we extended the functional genomics approach of signature-tagged mutagenesis to S. choleraesuis and pigs. When a test pool of 45 randomly signature-tagged null mutants was inoculated orally and intraperitoneally in pigs, one of the mutants that failed to colonize by either route was tagged in hilA. In the broad host range serovar S. typhimurium, hilA regulates invasion genes in the first pathogenicity island and is required for enteric but not systemic infections in mice experimentally infected with S. typhimurium. The pool of tagged S. choleraesuis null mutants was a complex mix inoculated in pigs. When pigs were challenged with an equal mixture of the hilA mutant and wild type bacteria, the hilA mutant was at a competitive disadvantaged (attenuated) in pigs inoculated orally but not in intraperitoneally inoculated pigs. Our data support that hilA in S. choleraesuis infections of pigs has a role in enteric but not systemic infections similar to that of S. typhimurium in the murine model of human typhoid fever. The role of hilA may be conserved across Salmonella serovars and host species.