Microbiota, Probiotic and Dietary Metabolite Control of Enteric Pathogen Virulence

项目摘要 来自微生物群、益生菌和饮食的关键代谢物可以抑制肠道病原体的毒力特性， 但它们的作用机制尚不清楚，限制了新抗感染药物的开发。确定 主要微生物群代谢产物（短链脂肪酸、芳香族氨基酸、胆汁酸）的作用机制 酸和其他），需要多学科的方法来生化鉴定代谢物-蛋白质靶标 并表征其对体内感染活性。因此，我的实验室将 在化学生物学，蛋白质组学和细菌基因编辑的创新方法，以阐明如何具体 代谢物减弱肠道病原体感染。更好地了解这些代谢物如何影响 细菌病原体的毒力特性应该揭示潜在的治疗靶点， 开发新的抗感染药物，以对抗动物和人类的细菌病原体。

PROJECT SUMMARY Key metabolites from microbiota, probiotics and diet can inhibit the virulence properties of enteric pathogens, but their mechanisms of action are unclear and limit the development of new anti-infectives. To determine the mechanism(s) of action of prominent microbiota metabolites (short chain fatty acids, aromatic amino acids, bile acids and others), multi-disciplinary approaches are needed to biochemically identify metabolite-protein targets in enteric pathogens and characterize their activity on infections in vivo. My laboratory will therefore employ innovative methods in chemical biology, proteomics and gene editing in bacteria to elucidate how specific metabolites attenuates enteric pathogen infections. A better understanding of how these metabolites affects the virulence properties of bacterial pathogens should reveal potential therapeutic targets and facilitate the development of new anti-infectives to combat bacterial pathogens in animals and humans.