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Project C09

Principal Investigator: Prof. Dr. Kai Papenfort

Probing the Role of Chemical Signalling in the Interplay of Gut Commensals, Pathogens, and their Phages.


Vibrio cholerae is the causative agent of the major human diarrheal disease, cholera. When

colonizing the human gut, V. cholerae interacts with dozens of commensal microorganisms and their secreted molecules. However, how these influence the production of V. cholerae’s virulence factors and the overall progression of the disease is only poorly understood. In addition, bacteriophages (or short phages) shape the infection process of V. cholerae and frequently quench cholera outbreaks in endemic settings. Yet it is unknown if and how other bacteria and signals play into this process.

In this project, we will investigate the interplay of V. cholerae with two of its major intestinal

competitors, i.e. Blautia obeum and Escherichia coli, as well as the temperate vibriophage VP882. We will focus on the role of three previously identified quorum sensing (QS) molecules, i.e. AI-2, CAI-1, and DPO, in this microbial community and study how genotoxic colibactin modulates the interaction among the three microbes, as well as the lifecycle of VP882. To this end, we will employ cutting-edge transcriptomics and metabolomics to record the response of the community members towards each other and to the individual signaling molecules. We will harness this information to design species-specific fluorescent reporter strains that will allow us to follow signal perception, integration, and QS output at the population and single cell level. Further, we will test if and how QS signals from other species modulate key regulatory functions such as biofilm formation, virulence gene expression, and phage escape, and we will extend these analyses into bacteria-derived genotoxic compounds including colibactin. Finally, we will aim to generate and characterize artificial QS activators to manipulate collective behaviours in V. cholerae.

Team C09