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

Jingzhe Guo, Wilhelmina T Van De Ven, Aleksandra Skirycz, Venkatesh P. Thirumalaikumar, Liping Zeng, Quanqing Zhang, Gerd Ulrich Balcke, Alain Tissier and Katayoon Dehesh ()
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Jingzhe Guo: University of California, Riverside
Wilhelmina T Van De Ven: University of California, Riverside
Aleksandra Skirycz: Boyce Thompson Institute
Venkatesh P. Thirumalaikumar: Boyce Thompson Institute
Liping Zeng: University of California, Riverside
Quanqing Zhang: Riverside
Gerd Ulrich Balcke: Department of Cell and Metabolic Biology; Weinberg 3
Alain Tissier: Department of Cell and Metabolic Biology; Weinberg 3
Katayoon Dehesh: University of California, Riverside

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-54501-w

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