Cooperative pathogenicity of enteropathogenic E. coli (EPEC) within mucosa-attached microcolonies

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Dynamic multicellular bacterial consortia intimately attached to the host’s small intestinal mucosal surface represent the hallmark of enteropathogenic E. coli (EPEC) pathogenicity. Despite their fundamental importance, the structural and spatial organization and the transcriptional heterogeneity, cooperative activity and communication between individual bacteria within these heterogeneous multicellular consortia have not yet been analyzed. Here, we therefore propose to employ established in vitro, ex vivo and in vivo models in combination with genetic reporter technology, competition experiments with isogenic EPEC mutants, highly innovative bacterial single cell transcriptomics and advanced imaging technologies to study the overall structural organization and functional interaction between bacteria, characterize the transcriptional heterogeneity within these consortia, and identify the mechanisms that underlie and account for the cooperative pathogenicity of EPEC. If successful, the obtained results are expected to significantly advance our understanding of the cooperative action of bacteria within multicellular consortia and its critical contribution to EPEC colonization, transmission and pathogenesis.