title: SopB, a protein required for virulence of Salmonella dublin, is an inositol phosphate phosphatase.
abstract: Several proteins secreted by enteric bacteria are thought to contribute to virulence by disturbing the signal transduction of infected cells. Here, we report that SopB, a protein secreted by Salmonella dublin, has sequence homology to mammalian inositol polyphosphate 4-phosphatases and that recombinant SopB has inositol phosphate phosphatase activity in vitro. SopB hydrolyzes phosphatidylinositol 3,4,5-trisphosphate, an inhibitor of Ca2+-dependent chloride secretion. In addition, SopB hydrolyzes inositol 1,3,4,5,6 pentakisphosphate to yield inositol 1,4,5, 6-tetrakisphosphate, a signaling molecule that increases chloride secretion indirectly by antagonizing the inhibition of chloride secretion by phosphatidylinositol 3,4,5-trisphosphate [Eckmann, L., Rudolf, M. T., Ptasznik, A., Schultz, C., Jiang, T., Wolfson, N., Tsien, R., Fierer, J., Shears, S. B., Kagnoff, M. F., et al. (1997) Proc. Natl. Acad. Sci. USA 94, 14456-14460]. Mutation of a conserved cysteine that abolishes phosphatase activity of SopB results in a mutant strain, S. dublin SB c/s, with decreased ability to induce fluid secretion in infected calf intestine loops. Moreover, HeLa cells infected with S. dublin SB c/s do not accumulate high levels of inositol 1,4,5,6-tetrakisphosphate that are characteristic of wild-type S. dublin-infected cells. Therefore, SopB mediates virulence by interdicting inositol phosphate signaling pathways.
authors.affiliation: Division of Hematology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO, 63110, USA.
authors.forename: F A
authors.initials: FA
authors.lastname: Norris
authors.forename: M P
authors.initials: MP
authors.lastname: Wilson
authors.forename: T S
authors.initials: TS
authors.lastname: Wallis
authors.forename: E E
authors.initials: EE
authors.lastname: Galyov
authors.forename: P W
authors.initials: PW
authors.lastname: Majerus
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002417:Cattle; D002645:Chickens; D017124:Conserved Sequence; D004912:Erythrocytes / Q000201:enzymology; D006367:HeLa Cells; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009504:Neutrophils / Q000382:microbiology / Q000502:physiology; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012475:Salmonella / Q000201:enzymology* / Q000235:genetics* / Q000472:pathogenicity; D013379:Substrate Specificity; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D007295:Inositol Phosphates; D011994:Recombinant Proteins; C060972:SopB protein, Bacteria; C489224:SopB protein, Salmonella