Identification of a Putative Salmonellaenterica Serotype Typhimurium Host Range Factor with Homology toIpaH and YopM by Signature-Tagged Mutagenesis

摘要

The genetic basis for the host adaptation of Salmonella serotypes is currently unknown. We have explored a new strategy to identify Salmonella enterica serotype Typhimurium (S. typhimurium) genes involved in host adaptation, by comparing the virulence of 260 randomly generated signature-tagged mutants during the oral infection of mice and calves. This screen identified four mutants, which were defective for colonization of only one of the two host species tested. One mutant, which only displayed a colonization defect during the infection of mice, was further characterized. During competitive infection experiments performed with the S. typhimurium wild type, the mutant was defective for colonization of murine Peyer's patches but colonized bovine Peyer's patches at the wild-type level. No difference in virulence between wild type and mutant was observed when calves were infected orally with 10¹⁰ CFU/animal. In contrast, the mutant possessed a sixfold increase in 50% lethal morbidity dose when mice were infected orally. The transposon in this mutant was inserted in a 2.9-kbpathogenicity islet, which is located between uvrB andyphK on the S. typhimurium chromosome. Thispathogenicity islet contained a single gene, termed slrP,with homology to ipaH of Shigella flexneri andyopM of Yersinia pestis. These data show thatcomparative screening of signature-tagged mutants in two animal speciescan be used for scanning the S. typhimurium genome forgenes involved in host adaptation.