The Gut Commensal Bacteroides thetaiotaomicron Exacerbates Enteric Infection through Modification of the Metabolic Landscape

Meredith M. Curtis, Zeping Hu, Claire Klimko, Sanjeev Narayanan, Ralph Deberardinis, Vanessa Sperandio. Cell Host & Microbe. 10 December 2014.

Speaker: Yang Fei (費暘)                                              Time: 15:15~16:00, May 20, 2015

Commentator: Dr. Jenn-Wei Chen (陳振暐 老師)      Place: Room 601

Abstract:

Gut microbes have been shown or proposed to have an impact on adipose tissue and liver fat storage, skeletal muscle energy metabolism, fat liver metabolism and hepatic steatosis, atherosclerosis and cardiovascular diseases, tissue lipid composition in the retina lens, periodontitis, behavior and motor activity, and enteroendocrine metabolism. The human pathogenEnterohemorrhagic E. coli (EHEC) colonizes the human colon, forming attaching and effacing (AE) lesions, invoking diarrhea, hemolytic uremic syndrome(HUS). The gut commensal Bacteroidesthetaiotaomicron encodes a number of glycoside hydrolases and polysaccharide lyases to alter sugar concentrations within the intestine. In this study, due to EHEC poorly infects mice, researchers used C. rodentium as an infection model which can develop AE lesions and damage on the intestinal epithelium in mice to study EHEC infection in the context of an altered microflora. They demonstrated that Bt enhances EHEC virulence through the Cra transcription factor. Moreover Bt increases succinate which can be sensed by Cra to activate virulence genes. In the presence of Bt, enteric infection disease prognosis and host pathology become worse and Bt regulates EHEC virulence by changing the metabolite landscape within the gut. In conclusion, Bt altering the metabolic landscape toward a gluconeogenic environment and secreting large amounts of the succinate metabolite within the intestine that is interpreted by the pathogen, through the transcription factor Cra to activate virulence gene expression and enhance disease susceptibility.

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