title: Host restriction of Salmonella enterica serotype Typhi is not caused by functional alteration of SipA, SopB, or SopD.
abstract: Salmonella enterica serotype Typhi is a strictly human adapted pathogen that does not cause disease in nonprimate vertebrate hosts, while Salmonella enterica serotype Typhimurium is a broad-host-range pathogen. Serotype Typhi lacks some of the proteins (effectors) exported by the invasion-associated type III secretion system that are required by serotype Typhimurium for eliciting fluid secretion and inflammation in bovine ligated ileal loops. We investigated whether the remaining serotype Typhi effectors implicated in enteropathogenicity (SipA, SopB, and SopD) are functionally exchangeable with their serotype Typhimurium homologues. Serotype Typhi elicited fluid accumulation in bovine ligated ileal loops at levels similar to those elicited by a noninvasive serotype Typhimurium strain (the sipA sopABDE2 mutant) or by sterile culture medium. However, introduction of the cloned serotype Typhi sipA, sopB, and sopD genes complemented the ability of a serotype Typhimurium sipA sopABDE2 mutant to elicit fluid secretion in bovine ligated ileal loops. Introduction of the cloned serotype Typhi sipA, sopB, and sopD genes increased the invasiveness of a serotype Typhimurium sipA sopABDE2 mutant for human colon carcinoma epithelial (HT-29 and T84) cells and bovine kidney (MDBK) cells. Translational fusions between the mature TEM-1 beta-lactamase reporter and SipA or SopD demonstrated that serotype Typhi translocates these effectors into host cells. We conclude that the inability of serotype Typhi to cause fluid accumulation in bovine ligated ileal loops is not caused by a functional alteration of its SipA, SopB, and SopD effector proteins with respect to their serotype Typhimurium homologues.
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, One Shields Ave., Davis, CA 95616-8645, USA.
authors.forename: Manuela
authors.initials: M
authors.lastname: Raffatellu
authors.forename: Yao-Hui
authors.initials: YH
authors.lastname: Sun
authors.forename: R Paul
authors.initials: RP
authors.lastname: Wilson
authors.forename: Quynh T
authors.initials: QT
authors.lastname: Tran
authors.forename: Daniela
authors.initials: D
authors.lastname: Chessa
authors.forename: Helene L
authors.initials: HL
authors.lastname: Andrews-Polymenis
authors.forename: Sara D
authors.initials: SD
authors.lastname: Lawhon
authors.forename: Josely F
authors.initials: JF
authors.lastname: Figueiredo
authors.forename: Renée M
authors.initials: RM
authors.lastname: Tsolis
authors.forename: L Garry
authors.initials: LG
authors.lastname: Adams
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Bäumler
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D002417:Cattle; D002478:Cells, Cultured; D003001:Cloning, Molecular; D005798:Genes, Bacterial / Q000502:physiology*; D005816:Genetic Complementation Test; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D009154:Mutation; D021381:Protein Transport; D012485:Salmonella typhi / Q000235:genetics / Q000472:pathogenicity*; D012486:Salmonella typhimurium / Q000235:genetics / Q000472:pathogenicity; D013045:Species Specificity
chemical_list: D001426:Bacterial Proteins; D008840:Microfilament Proteins; C118287:SipA protein, Salmonella; C116105:SopD protein, Salmonella; C489224:SopB protein, Salmonella