Global characterization of phenotypic heterogeneity in enteropathogenic Escherichia coli
2Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Israel
Enteropathogenic Escherichia coli (EPEC) are highly abundant diarrheal pathogens of young children in the developing countries. While most studies refer to typical-EPEC bacteria as a homogenic group, a previous study revealed that these bacteria have two co-existing genetically identical morphotypes when moved from host-mimicking to non-host-mimicking environments: one that remains virulent and another that becomes avirulent. In order to characterize the two morphotypes at the single cell transcriptome-wide level, a high-throughput methodology was developed and applied to EPEC bacteria belonging to the two morphotypes grown under the exact same conditions. Our methodology reveled a clear virulence signature of the virulent morphotype and enabled to identify new virulent genes in previously unannotated regions of the EPEC genome. When applied to EPEC bacteria grown under various host-related environments such as in the presence of microbiome metabolites or in anerobic conditions, our methodology highlighted with unprecedented discriminating power the genes important for virulence in each of the growth conditions. Our approach enables to take advantage of spontaneous phenotypic heterogeneity in genetically identical bacteria and reveal uncharacterized virulence genes, leading to identification of new virulence strategies of pathogenic bacteria. More generally, our approach should enable to reveal previously uncharacterized bacterial phenotypes.