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Cell Rep ; 43(5): 114154, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38669142

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.


Subject(s)
Biofilms , Cyclic GMP , Pseudomonas aeruginosa , Purines , Pseudomonas aeruginosa/metabolism , Pseudomonas aeruginosa/physiology , Biofilms/growth & development , Cyclic GMP/metabolism , Cyclic GMP/analogs & derivatives , Purines/metabolism , Purines/pharmacology , Bacterial Proteins/metabolism
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