SOPB, A PROTEIN REQUIRED FOR VIRULENCE OF SALMONELLA-DUBLIN, IS AN INOSITOL PHOSPHATE PHOSPHATASE

Several proteins secreted by enteric bacteria are thought to contribut e 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-phosphatas es and that recombinant SopB has inositol phosphate phosphatase activi ty 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 se cretion indirectly by antagonizing the inhibition of chloride secretio n by phosphatidylinositol 3,4,5-trisphosphate [Eckmann, L., Rudolf, M. T., Ptasznik, A., Schultz, C., Jiang, T., Wolfson, N., Tsien, R., Fie rer, J., Shears, S. B., Kagnoff, M. F., et al. (1997) Proc. Natl. Acad . Sci. USA 94, 14456-14460], Mutation of a conserved cysteine that abo lishes phosphatase activity of SopB results in a mutant strain, S. dub lin SE c/s, with decreased ability to induce fluid secretion in infect ed calf intestine loops. Moreover, HeLa cells infected with S. dublin SE c/s do not accumulate high levels of inositol 1,4,5,6-tetrakisphosp hate that are characteristic of wild-type S. dublin-infected cells. Th erefore, SopB mediates virulence by interdicting inositol phosphate si gnaling pathways.