Quantitative input-output dynamics of a c-di-GMP signal transduction cascade in Vibrio cholerae. Author Andrew Bridges, Jojo Prentice, Chenyi Fei, Ned Wingreen, Bonnie Bassler Publication Year 2022 Type Journal Article Abstract Bacterial biofilms are multicellular communities that collectively overcome environmental threats and clinical treatments. To regulate the biofilm lifecycle, bacteria commonly transduce sensory information via the second messenger molecule cyclic diguanylate (c-di-GMP). Using experimental and modeling approaches, we quantitatively capture c-di-GMP signal transmission via the bifunctional polyamine receptor NspS-MbaA, from ligand binding to output, in the pathogen Vibrio cholerae. Upon binding of norspermidine or spermidine, NspS-MbaA synthesizes or degrades c-di-GMP, respectively, which, in turn, drives alterations specifically to biofilm gene expression. A long-standing question is how output specificity is achieved via c-di-GMP, a diffusible molecule that regulates dozens of effectors. We show that NspS-MbaA signals locally to specific effectors, sensitizing V. cholerae to polyamines. However, local signaling is not required for specificity, as changes to global cytoplasmic c-di-GMP levels can selectively regulate biofilm genes. This work establishes the input-output dynamics underlying c-di-GMP signaling, which could be useful for developing bacterial manipulation strategies. Keywords Biofilms, Vibrio cholerae, Signal Transduction, Cyclic GMP Journal PLoS Biol Volume 20 Issue 3 Pages e3001585 Date Published 2022 Mar ISSN Number 1545-7885 DOI 10.1371/journal.pbio.3001585 Alternate Journal PLoS Biol PMCID PMC8967002 PMID 35302986 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML