Date of Award
Doctor of Philosophy (PhD)
Thomas A Hughes
David M Feliciano
Cyclic di-nucleotides are important secondary signaling molecules in bacteria that regulate a wide range of processes. Recently, the role of these molecules has expanded to the eukaryotic domain where they act in modulating the innate immune response. In this study, we have shown that Caenorhabditis elegans are able to detect and are attracted towards numerous signaling molecules produced by Vibrio cholerae, even though this bacterium kills the host at a high rate. Of these molecules, it seems that CDNs are playing an important role, specifically the 3’,5’-cyclic diguanylate (c-di-GMP), and the recently described hybrid molecule produced by V. cholerae, c-GMP-AMP (c-GAMP). The chemoattraction of C. elegans towards these molecules occur in a concentration dependent manner. However, c-di-GMP was the only CDN present in V. cholerae cell lysate or supernatant, revealing its importance in this novel communication pathway. C-di-GMP is sensed through C. elegans olfactory AWC neurons which then evokes a series of signal transduction pathways that lead to reduced activity of two key stress response transcription factors, SKN-1 and HSF-1, and a weakened innate immunity. Taken together, our study elucidates the role of c-di-GMP in interkingdom communication, i.e. bacteria produce c-di-GMP to attract a host and impair its immune response, which in turn promotes bacterial invasion and survival.
Angeloni, Joseph, "Interkingdom Communication: The Role of Cyclic Di-nucleotides, Specifically 3’,5’-Cyclic Diguanylate, in Attraction and Immunomodulation of Caenorhabditis elegans" (2020). All Dissertations. 2606.