Mechanism and inflammatory impact of extracellular ATP signalling in gut bacteria

We showed that high extracellular ATP (eATP) causes acute inflammation during intestinal infection and that high eATP is present in the gut lumen during infectious and inflammatory diseases.

We now discovered that, just as eukaryotic cells, gut bacteria that are exposed to this eATP use it as environmental signal.

In E. coli eATP induces a shift in the transcriptional and metabolic landscape.Here we will 1) identify the genes necessary to sense and respond to eATP in bacteria, with focus on the eATP receptor; 2) decipher how the response to eATP alters bacterial physiology and virulence and 3) assess its impact on intestinal inflammation.We have collected a wealth of biochemical, genetic and bioinformatic data to map the eATP sensing and response network in E. coli.

We will predict species that can sense eATP by comparative genomics.

We will perform RNAseq and metabolomics in commensal and pathogenic gut bacteria from in vitro and in vivo samples and assess the inflammatory effect of this eATP-driven response in animal models.We will provide the first example of a bacterial response to eATP, which allows inter-kingdom signalling in the inflamed gut, and supply a molecular and phylogenetic framework to this discovery.

We will reveal novel molecular mechanisms controlling the development of infectious and inflammatory diseases, which are targets for anti-microbial or anti-inflammatory therapy.This is a 4-years project for two postdocs (100% and 40%) and a PhD student (25%).