Title | Quantitative input-output dynamics of a c-di-GMP signal transduction cascade in Vibrio cholerae. |
Publication Type | Journal Article |
Year of Publication | 2022 |
Authors | Bridges, AA, Prentice, JA, Fei, C, Wingreen, NS, Bassler, BL |
Journal | PLoS Biol |
Volume | 20 |
Issue | 3 |
Pagination | e3001585 |
Date Published | 2022 03 |
ISSN | 1545-7885 |
Keywords | Biofilms, Cyclic GMP, Signal Transduction, Vibrio cholerae |
Abstract | <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> |
DOI | 10.1371/journal.pbio.3001585 |
Alternate Journal | PLoS Biol |
PubMed ID | 35302986 |
PubMed Central ID | PMC8967002 |
Grant List | K99 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 |