Identification of a putative Salmonella enterica serotype typhimurium hostrange factor with homology to IpaH and YopM by signature-tagged mutagenesis

The genetic basis for the host adaptation of Salmonella serotypes is curren tly unknown. We have explored a new strategy to identify Salmonella enteric a serotype Typhimurium (S. typhimurium) genes involved in host adaptation, by comparing the virulence of 260 randomly generated signature-tagged mutan ts during the oral infection of mice and calves. This screen identified fou r mutants, which were defective for colonization of only one of the two hos t species tested. One mutant,,which only displayed a colonization defect du ring the infection of mice, was further characterized. During competitive i nfection experiments performed with the S. typhimurium wild type, the mutan t was defective for colonization of murine Peyer's patches but colonized bo vine Peyer's patches at the wild-type level. No difference in virulence bet ween wild type and mutant was observed when calves were infected orally wit h 10(10) CFU/animal. In contrast, the mutant possessed a sixfold increase i n 50% lethal morbidity dose when mice were infected orally. The transposon in this mutant was inserted in a 2.9-kb pathogenicity islet, which is locat ed between uvrB and yphK on the S. typhimurium chromosome. This pathogenici ty islet contained a single gene, termed slrP, with homology to ipaH of Shi gella flexneri and yopM of Yersinia pestis. These data show that comparativ e screening of signature-tagged mutants in two animal species can be used f or scanning the S. typhimurium genome for genes involved in host adaptation .