An evolutionarily conserved metabolite inhibits biofilm formation in Escherichia coli K-12

Nat Commun. 2024 Nov 21;15(1):10079. doi: 10.1038/s41467-024-54501-w.

Abstract

Methylerythritol cyclodiphosphate (MEcPP) is an intermediate in the biosynthesis of isoprenoids in plant plastids and in bacteria, and acts as a stress signal in plants. Here, we show that MEcPP regulates biofilm formation in Escherichia coli K-12 MG1655. Increased MEcPP levels, triggered by genetic manipulation or oxidative stress, inhibit biofilm development and production of fimbriae. Deletion of fimE, encoding a protein known to downregulate production of adhesive fimbriae, restores biofilm formation in cells with elevated MEcPP levels. Limited proteolysis-coupled mass spectrometry (LiP-MS) reveals that MEcPP interacts with the global regulatory protein H-NS, which is known to repress transcription of fimE. MEcPP prevents the binding of H-NS to the fimE promoter. Therefore, our results indicate that MEcPP can regulate biofilm formation by modulating H-NS activity and thus reducing fimbriae production. Further research is needed to test whether MEcPP plays similar regulatory roles in other bacteria.

MeSH terms

  • Biofilms* / drug effects
  • Biofilms* / growth & development
  • Erythritol / analogs & derivatives
  • Erythritol / metabolism
  • Erythritol / pharmacology
  • Escherichia coli K12* / drug effects
  • Escherichia coli K12* / genetics
  • Escherichia coli K12* / metabolism
  • Escherichia coli K12* / physiology
  • Escherichia coli Proteins* / genetics
  • Escherichia coli Proteins* / metabolism
  • Fimbriae, Bacterial* / genetics
  • Fimbriae, Bacterial* / metabolism
  • Gene Expression Regulation, Bacterial*
  • Oxidative Stress
  • Promoter Regions, Genetic

Substances

  • Escherichia coli Proteins
  • Erythritol