SopB, a protein required for virulence of Salmonella dublin, is an inositol phosphate phosphatase.
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.
Norris
F A
FA
Division of Hematology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO, 63110, USA.
Wilson
M P
MP
Wallis
T S
TS
Galyov
E E
EE
Majerus
P W
PW
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
D001426:Bacterial Proteins; D007295:Inositol Phosphates; D011994:Recombinant Proteins; C060972:SopB protein, Bacteria; C489224:SopB protein, Salmonella