Recent advances in single cell technologies revealed that a clonal bacterial population is not a sum of identical bacterial cells but instead gathers individuals with potentially distinct phenotypes. This phenomenon, termed phenotypic heterogeneity, appears to be particularly suitable for efficient adaptation of bacteria to their environments. Intriguingly, the role of phenotypic heterogeneity in bacterial infectious process has been poorly investigated despite the fact that pathogens transit through several dynamic and heterogeneous environments during their lifecycle. In this project, we plan to develop and use tools in order to identify genes associated with phenotypic heterogeneity during an infection. For this purpose, we will use the natural mouse pathogen Citrobacter rodentium that shares many virulence properties with intestinal pathogenic Escherichia coli responsible for acute or chronic diseases in humans. We will construct and screen a library reporting transcriptional activities in single cells to identify genes that are heterogeneously expressed during the initial colonization stage which is decisive for the infection outcome. The discovery of genes with noisy expression in vivo would open the possibility to start functional studies in order to explore if phenotypic heterogeneity is a hallmark in host adaptation of pathogens.

Financement

Projet INRAE - Département MICA