Local control: a hub-based model for the c-di-GMP network

mSphere. 2024 May 29;9(5):e0017824. doi: 10.1128/msphere.00178-24. Epub 2024 Apr 9.

Abstract

The genome of Pseudomonas fluorescens encodes >50 proteins predicted to play a role in bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP)-mediated biofilm formation. We built a network representation of protein-protein interactions and extracted key information via multidimensional scaling (i.e., principal component analysis) of node centrality measures, which measure features of proteins in a network. Proteins of different domain types (diguanylate cyclase, dual domain, phosphodiesterase, PilZ) exhibit unique network behavior and can be accurately classified by their network centrality values (i.e., roles in the network). The predictive power of protein-protein interactions in biofilm formation indicates the possibility of localized pools of c-di-GMP. A regression model showed a statistically significant impact of protein-protein interactions on the extent of biofilm formation in various environments. These results highlight the importance of a localized c-di-GMP signaling, extend our understanding of signaling by this second messenger beyond the current "Bow-tie Model," support a newly proposed "Hub Model," and suggest future avenues of investigation.

Keywords: Lap system; Pseudomonas fluorescens; c-di-GMP; network.

MeSH terms

  • Bacterial Proteins* / genetics
  • Bacterial Proteins* / metabolism
  • Biofilms* / growth & development
  • Cyclic GMP* / analogs & derivatives
  • Cyclic GMP* / metabolism
  • Escherichia coli Proteins
  • Gene Expression Regulation, Bacterial
  • Phosphorus-Oxygen Lyases
  • Protein Interaction Maps
  • Pseudomonas fluorescens* / genetics
  • Pseudomonas fluorescens* / metabolism

Substances

  • Cyclic GMP
  • bis(3',5')-cyclic diguanylic acid
  • Bacterial Proteins
  • diguanylate cyclase
  • Phosphorus-Oxygen Lyases
  • Escherichia coli Proteins