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

Andrew A. Bridges, Jojo A. Prentice, Chenyi Fei, Ned S. Wingreen, Bonnie L. Bassler

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


AU Bacterial: Pleaseconfirmthatallheadinglevelsarerepresentedcorrectly 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.

Original languageEnglish (US)
Article numbere3001585
JournalPLoS biology
Issue number3
StatePublished - Mar 2022

All Science Journal Classification (ASJC) codes

  • General Agricultural and Biological Sciences
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology
  • General Neuroscience


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