Identification of a Putative <i>Salmonella enterica</i> Serotype Typhimurium Host Range Factor with Homology to IpaH and YopM by Signature-Tagged Mutagenesis

TLDR

The genetic basis for host adaptation of Salmonella serotypes remains unknown. The study aimed to identify S. Typhimurium genes involved in host adaptation by comparing virulence of 260 signature‑tagged mutants in mice and calves. Researchers generated 260 random signature‑tagged mutants, assessed their virulence during oral infection of mice and calves, and performed competitive infection assays to characterize a mouse‑specific colonization defect.

Abstract

ABSTRACT 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 10 10 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-kb pathogenicity islet, which is located between uvrB and yphK on the S. typhimurium chromosome. This pathogenicity islet contained a single gene, termed slrP , with homology to ipaH of Shigella flexneri and yopM of Yersinia pestis . These data show that comparative screening of signature-tagged mutants in two animal species can be used for scanning the S. typhimurium genome for genes involved in host adaptation.