title: The Salmonella enterica serotype typhimurium effector proteins SipA, SopA, SopB, SopD, and SopE2 act in concert to induce diarrhea in calves.
abstract: Salmonella enterica serotype Typhimurium requires a functional type III secretion system encoded by Salmonella pathogenicity island 1 (SPI1) to cause diarrhea. We investigated the role of genes encoding secreted target proteins of the SPI1-associated type III secretion system for enteropathogenicity in calves. Salmonella serotype Typhimurium strains having mutations in sptP, avrA, sspH1, or slrP induced fluid secretion in the bovine ligated ileal loop model at levels similar to that of the wild type. In contrast, mutations in sipA, sopA, sopB, sopD, or sopE2 significantly reduced fluid accumulation in bovine ligated ileal loops at 8 h postinfection. A strain carrying mutations in sipA, sopA, sopB, sopD, and sopE2 (sipA sopABDE2 mutant) caused the same level of fluid accumulation in bovine ligated ileal loops as a strain carrying a mutation in sipB, a SPI1 gene required for the translocation of effector proteins into host cells. A positive correlation was observed between the severity of histopathological lesions detected in the ileal mucosa and the levels of fluid accumulation induced by the different mutants. After oral infection of calves, the Salmonella serotype Typhimurium sipAsopABDE2 mutant caused only mild diarrhea and was more strongly attenuated than strains having only single mutations. These data demonstrate that SipA, SopA, SopB, SopD, and SopE2 are major virulence factors responsible for diarrhea during Salmonella serotype Typhimurium infection of calves.
authors.affiliation: Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, Texas 77843-4467, USA.
authors.forename: Shuping
authors.initials: S
authors.lastname: Zhang
authors.forename: Renato L
authors.initials: RL
authors.lastname: Santos
authors.forename: Renee M
authors.initials: RM
authors.lastname: Tsolis
authors.forename: Silke
authors.initials: S
authors.lastname: Stender
authors.forename: Wolf-Dietrich
authors.initials: WD
authors.lastname: Hardt
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Bäumler
authors.forename: L Garry
authors.initials: LG
authors.lastname: Adams
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D002417:Cattle; D003967:Diarrhea / Q000453:epidemiology / Q000276:immunology / Q000382:microbiology*; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D007082:Ileum / Q000276:immunology / Q000473:pathology; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D016296:Mutagenesis; D010581:Peyer's Patches / Q000276:immunology; D012480:Salmonella Infections / Q000453:epidemiology / Q000276:immunology / Q000382:microbiology*; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D020662:Guanine Nucleotide Exchange Factors; D008840:Microfilament Proteins; C118287:SipA protein, Salmonella; C060972:SopB protein, Bacteria; C116105:SopD protein, Salmonella; C436324:SopE2 protein, Salmonella typhimurium; C419942:Spi1 protein, Salmonella; C060971:SopA protein, Bacteria; C489224:SopB protein, Salmonella