Abstract
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.
Highlights
Cyclic di-nucleotides are important secondary signaling molecules in bacteria that regulate a wide range of processes
We reported that watersoluble cranberry extract protects C. elegans from killing by different pathogenic bacteria, including V. cholerae, Pseudomonas aeruginosa, Salmonella typhimurium, Enterococcus faecalis, and Staphylococcus aureus[16]
A simple choice index (CI) assay was performed with the N2 wild type C. elegans over the course of 2 h to test whether the worms prefer the pathogenic V. cholerae wild type strain C6706 rather than E. coli OP50, the common food source for C. elegans used in the lab
Summary
Cyclic di-nucleotides are important secondary signaling molecules in bacteria that regulate a wide range of processes. While the AIs are extracellular signaling molecules, bacteria use a range of nucleotide-based intracellular signaling molecules known as second messengers to regulate physiological responses to cope with a changing environment. Molecules such as cyclic adenosine 3′,5′-monophosphate (cAMP) and guanosine pentaphosphate or tetraphosphate ((p) ppGpp) have been well studied for almost 50 years[2,3]. The second CDN, 3′,5′-cyclic diadenylate (c-di-AMP), is mainly found in Gram-positive bacteria It has been characterized as an essential signaling molecule that regulates cell wall homeostasis, potassium ion channels, DNA integrity, as well as biofilm formation and virulence[7]. These signals can be detected by the endoplasmicreticulum-resident protein STING (stimulator of interferon genes) in humans and mediate the type I interferon immune response[12,13]
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