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Cyclic di-nucleotides are important secondary signaling molecules in bacteria that regulate a wide range of processes. In this study, we found that  Caenorhabditis elegans  can detect and are attracted to multiple signal molecules produced by  Vibrio cholerae , specifically the 3′,5′-cyclic diguanylate (c-di-GMP), even though this bacterium kills the host at a high rate. 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 weakened innate immunity. Taken together, our study elucidates the role of c-di-GMP in interkingdom communication. For  C. elegans , bacterial c-di-GMP may serve as a cue that they can use to detect food. On the other hand, preexposure to low concentrations of c-di-GMP may impair their immune response, which could facilitate bacterial invasion and survival.

Bacterial second messenger 3′,5′-cyclic diguanylate attracts Caenorhabditis elegans and suppresses its immunity