title: Novel determinants of intestinal colonization of Salmonella enterica serotype typhimurium identified in bovine enteric infection.
abstract: Cattle are naturally infected with Salmonella enterica serotype Typhimurium and exhibit pathological features of enteric salmonellosis that closely resemble those in humans. Cattle are the most relevant model of gastrointestinal disease resulting from nontyphoidal Salmonella infection in an animal with an intact microbiota. We utilized this model to screen a library of targeted single-gene deletion mutants to identify novel genes of Salmonella Typhimurium required for survival during enteric infection. Fifty-four candidate mutants were strongly selected, including numerous mutations in genes known to be important for gastrointestinal survival of salmonellae. Three genes with previously unproven phenotypes in gastrointestinal infection were tested in bovine ligated ileal loops. Two of these mutants, STM3602 and STM3846, recapitulated the phenotype observed in the mutant pool. Complementation experiments successfully reversed the observed phenotypes, directly linking these genes to the colonization defects of the corresponding mutant strains. STM3602 encodes a putative transcriptional regulator that may be involved in phosphonate utilization, and STM3846 encodes a retron reverse transcriptase that produces a unique RNA-DNA hybrid molecule called multicopy single-stranded DNA. The genes identified in this study represent an exciting new class of virulence determinants for further mechanistic study to elucidate the strategies employed by Salmonella to survive within the small intestines of cattle.
authors.affiliation: Department of Large Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, USA.
authors.forename: Johanna R
authors.initials: JR
authors.lastname: Elfenbein
authors.forename: Tiana
authors.initials: T
authors.lastname: Endicott-Yazdani
authors.forename: Steffen
authors.initials: S
authors.lastname: Porwollik
authors.forename: Lydia M
authors.initials: LM
authors.lastname: Bogomolnaya
authors.forename: Pui
authors.initials: P
authors.lastname: Cheng
authors.forename: Jinbai
authors.initials: J
authors.lastname: Guo
authors.forename: Yi
authors.initials: Y
authors.lastname: Zheng
authors.forename: Hee-Jeong
authors.initials: HJ
authors.lastname: Yang
authors.forename: Marissa
authors.initials: M
authors.lastname: Talamantes
authors.forename: Christine
authors.initials: C
authors.lastname: Shields
authors.forename: Aimee
authors.initials: A
authors.lastname: Maple
authors.forename: Yury
authors.initials: Y
authors.lastname: Ragoza
authors.forename: Kimberly
authors.initials: K
authors.lastname: DeAtley
authors.forename: Tyler
authors.initials: T
authors.lastname: Tatsch
authors.forename: Ping
authors.initials: P
authors.lastname: Cui
authors.forename: Katharine D
authors.initials: KD
authors.lastname: Andrews
authors.forename: Michael
authors.initials: M
authors.lastname: McClelland
authors.forename: Sara D
authors.initials: SD
authors.lastname: Lawhon
authors.forename: Helene
authors.initials: H
authors.lastname: Andrews-Polymenis
mesh_terms: D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000382:microbiology*; D004195:Disease Models, Animal; D005759:Gastroenteritis / Q000382:microbiology* / Q000662:veterinary; D017353:Gene Deletion; D005816:Genetic Complementation Test; D005820:Genetic Testing; D012481:Salmonella Infections, Animal / Q000382:microbiology*; D012486:Salmonella typhimurium / Q000235:genetics / Q000472:pathogenicity*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D037521:Virulence Factors
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