Quantitative input-output dynamics of a c-di-GMP signal transduction cascade in Vibrio cholerae.

TitleQuantitative input-output dynamics of a c-di-GMP signal transduction cascade in Vibrio cholerae.
Publication TypeJournal Article
Year of Publication2022
AuthorsBridges, AA, Prentice, JA, Fei, C, Wingreen, NS, Bassler, BL
JournalPLoS Biol
Date Published2022 Mar
KeywordsBiofilms, Cyclic GMP, Signal Transduction, Vibrio cholerae

<p>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.</p>

Alternate JournalPLoS Biol
PubMed ID35302986
PubMed Central IDPMC8967002
Grant ListK99 AI158939 / AI / NIAID NIH HHS / United States
R01 GM082938 / GM / NIGMS NIH HHS / United States
R21 AI146223 / AI / NIAID NIH HHS / United States
R37 GM065859 / GM / NIGMS NIH HHS / United States
DRG-2302-17 / HHMI / Howard Hughes Medical Institute / United States