Environmental purines decrease Pseudomonas aeruginosa biofilm formation by disrupting c-di-GMP metabolism

Corey Kennelly; Peter Tran; Arthur Prindle

doi:10.1016/j.celrep.2024.114154

Environmental purines decrease Pseudomonas aeruginosa biofilm formation by disrupting c-di-GMP metabolism

Cell Rep. 2024 Apr 25;43(5):114154. doi: 10.1016/j.celrep.2024.114154. Online ahead of print.

Authors

Corey Kennelly¹, Peter Tran², Arthur Prindle³

Affiliations

¹ Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Center for Synthetic Biology, Northwestern University, Evanston, IL 60208, USA.
² Center for Synthetic Biology, Northwestern University, Evanston, IL 60208, USA; Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL 60208, USA.
³ Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Center for Synthetic Biology, Northwestern University, Evanston, IL 60208, USA; Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL 60208, USA. Electronic address: arthur.prindle@northwestern.edu.

PMID: 38669142
DOI: 10.1016/j.celrep.2024.114154

Abstract

Cyclic di-guanosine monophosphate (c-di-GMP) is a bacterial second messenger that governs the lifestyle switch between planktonic and biofilm states. While substantial investigation has focused on the proteins that produce and degrade c-di-GMP, less attention has been paid to the potential for metabolic control of c-di-GMP signaling. Here, we show that micromolar levels of specific environmental purines unexpectedly decrease c-di-GMP and biofilm formation in Pseudomonas aeruginosa. Using a fluorescent genetic reporter, we show that adenosine and inosine decrease c-di-GMP even when competing purines are present. We confirm genetically that purine salvage is required for c-di-GMP decrease. Furthermore, we find that (p)ppGpp prevents xanthosine and guanosine from producing an opposing c-di-GMP increase, reinforcing a salvage hierarchy that favors c-di-GMP decrease even at the expense of growth. We propose that purines can act as a cue for bacteria to shift their lifestyle away from the recalcitrant biofilm state via upstream metabolic control of c-di-GMP signaling.

Keywords: CP: Microbiology; Pseudomonas aeruginosa; bacteria; biofilms; c-di-GMP; microbiology; nucleotide signaling; purines.