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.
Original language | English (US) |
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Article number | 114154 |
Journal | Cell reports |
Volume | 43 |
Issue number | 5 |
DOIs | |
State | Published - May 28 2024 |
Funding
We thank Stephen Lander and Claire Phoumyvong for comments during the writing of this manuscript and members of the Prindle lab for their support. We thank Colin Manoil for MPAO1, Tim Tolker-Nielsen for pCdrA-GFP(ASV)C, and Kelly Bachta and Alan Hauser for S17-1 \u03BBpir and SM10 \u03BBpir E. coli and PAK and PA14 P. aeruginosa, as well as pEXG2, pminiCTX-1, and pFLP2 plasmids. We are grateful for the generous support from the David and Lucile Packard Foundation ( 2018\u201368055 ), the Army Research Office ( W911NF-19-1-0136 ), Pew Charitable Trusts ( 2019-A-06953 ), the National Science Foundation ( NSF 2239567 ), the National Institutes of Health ( 1R35GM147170-01 ), and a Dr. John N. Nicholson Fellowship from Northwestern University. We thank Stephen Lander and Claire Phoumyvong for comments during the writing of this manuscript and members of the Prindle lab for their support. We thank Colin Manoil for MPAO1, Tim Tolker-Nielsen for pCdrA-GFP(ASV)C, and Kelly Bachta and Alan Hauser for S17-1 \u03BBpir and SM10 \u03BBpir E. coli and PAK and PA14 P. aeruginosa, as well as pEXG2, pminiCTX-1, and pFLP2 plasmids. We are grateful for the generous support from the David and Lucile Packard Foundation (2018\u201368055), the Army Research Office (W911NF-21-1-0291), Pew Charitable Trusts (2019-A-06953), the National Science Foundation (NSF 2239567), the National Institutes of Health (1R35GM147170-01), and a Dr. John N. Nicholson Fellowship from Northwestern University. Conceptualization, C.K. and A.P.; investigation, C.K.; writing \u2013 original draft, C.K.; writing \u2013 review & editing, C.K. P.T. and A.P.; visualization, C.K. and P.T.; supervision, A.P.; funding acquisition, C.K. and A.P. The authors declare no competing interests.
Keywords
- CP: Microbiology
- Pseudomonas aeruginosa
- bacteria
- biofilms
- c-di-GMP
- microbiology
- nucleotide signaling
- purines
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology