The Role of Eiiabman and Ccpa in the Carbohydrate Regulation of Urease Expression in Streptococcus Salivarius

Urea hydrolysis by Streptococcus salivarius urease is the major alkali producing machinery in the oral cavity, which is critical for dental caries prevention. Urease expression in S. salivarius 57.1 is induced by growing at acidic pH and under sugar excess, under which conditions ammonia production via ureolysis is most needed for neutralizing excess amounts of acids and providing an additional nitrogen nutrient for growth. Our studies demonstrated that the pH regulation of the S. salivarius urease operon is governed by CodY and GlnR. At pH 7, CodY inhibits urease expression whereas GlnR activates the expression at pH 5.5. The goal of this proposal is to define factors which participate in the carbohydrate regulation of urease expression. By using an isogenic mutant that is deficient in the enzyme I of the phosphoenolpyruvate:sugar phosphotransferase system (PTS) and a 2-deoxyglucose resistant mutant that is defective in the enzyme IIAB for mannose (EIIABMan), our studies found that PTS-mediated phosphorylation inhibits urease expression and the PTS-directed regulation is likely to be mediated by EIIABMan. Furthermore, inactivation of catabolite control protein A (CcpA) upregulates urease expression. Taken together, PTS and CcpA likely influence carbohydrate-mediated regulation of urease expression. In this proposal, we will first investigate the impact of PTS-mediated phosphorylation on urease expression and the role of EIIABMan in this process. How CcpA participates in urease regulation will also be analyzed. The information obtained from this proposal will provide valuable insights into the regulatory networks that link carbon metabolism, nitrogen metabolism and acid tolerance in S. salivarius. Knowledge on the expression regulation of the S. salivarius urease operon will set a foundation for the development of therapeutic strategies that seek to modulate the alkali generation potential of dental plaque for caries control.

Project ID:PC10701-0295
External Project ID:MOST105-2320-B182-015-MY3