title: 'Form variation' of the O12 antigen is critical for persistence of Salmonella Typhimurium in the murine intestine.
abstract: Salmonella enterica subspecies I serotypes are responsible for the vast majority of salmonellosis in mammals and birds, yet only a few factors specific to this group that allow them to persist in this niche have been identified. We show that STM0557, a S. enterica subspecies I-specific gene encoding an inner membrane protein, is critical for faecal shedding and intestinal persistence of S. enterica serotype Typhimurium ATCC14028 in Salmonella-resistant mice, but mutations in this gene do not diminish short-term intestinal colonization or invasion of cultured epithelial cells. STM0557 and two neighbouring genes, located on a pathogenicity island termed SPI-16, resemble genes of the gtrA,B, gtr(type) cluster in seroconverting bacteriophages. In general, the gtr genes encode proteins responsible for serotype conversion of the infected bacterium by addition glucose residues to repeating O-antigen subunits of lipopolysaccharide (LPS). In lysogenized Shigella, such modifications have been previously shown to be constitutively expressed and to facilitate invasion of host cells. We show that serotype Typhimurium gtr orthologues, STM0557-0559, are responsible for 'form variation' or glucosylation of the O12 antigen galactose (4 position) to generate the 12-2 variant. Form variation in Typhimurium is not constitutive, but occurred upon exposure and during intracellular growth of serotype Typhimurium in J774 macrophages. Our data suggest that the 12-2 antigen is a S. enterica subspecies I-specific LPS modification that enhances long-term intestinal colonization, and is in contrast to the role of O-antigen variation described for Shigella.
authors.affiliation: Department of Microbial and Molecular Pathogenesis, College of Medicine, Texas A&M University System Health Science Center, College Station, TX 77843-1114, USA.
authors.forename: Lydia M
authors.initials: LM
authors.lastname: Bogomolnaya
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Santiviago
authors.forename: Hee-Jeong
authors.initials: HJ
authors.lastname: Yang
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Baumler
authors.forename: Helene L
authors.initials: HL
authors.lastname: Andrews-Polymenis
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D003001:Cloning, Molecular; D004269:DNA, Bacterial / Q000235:genetics; D017353:Gene Deletion; D005798:Genes, Bacterial; D044404:Genomic Islands; D006801:Humans; D007422:Intestines / Q000382:microbiology*; D008264:Macrophages / Q000382:microbiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D009154:Mutation; D019081:O Antigens / Q000235:genetics / Q000378:metabolism*; D012481:Salmonella Infections, Animal / Q000382:microbiology*; D012486:Salmonella typhimurium / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D013045:Species Specificity; D014774:Virulence
chemical_list: D004269:DNA, Bacterial; D008565:Membrane Proteins; D019081:O Antigens