Prof. Gad Frankel

27 April 2017

IFR Lecture Theatre

Speaker: Prof. Gad Frankel, Imperial College, London

Hosted by: Ian Charles

The mouse pathogen Citrobacter rodentium, a model organism to study infection with human pathogenic E. coli, triggers effacement of the brush border microvilli, colitis, hyperplasia and dysbiosis. We investigated the impact of infection with antibiotic resistant C. rodentium on intestinal epithelial cells (IECs) in vivo using, isobaric labelling proteomics, targeted metabolomics, lipidomics and in vivo imaging.

One of the major signatures of infection was re-programming metabolism in infected cells, including inhibition of central metabolism and mitochondrial functions, as well as activation of creatine, phosphocreatine, spermidine and cholesterol biosynthetic pathways. Concomitant with these changes, we detected reduction of butyrate-producing commensal bacteria and a bloom of proteobacteria, which could metabolise cholesterol. Selective antibiotic pressure at the peak of the infection affected tissue septicity of C. rodentium. Taken together, our data show how the host, the pathogen and the microbiota interact to produce a novel ecological gut environment that benefits the pathogen.

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