title: Cyclic-di-GMP levels affect Pseudomonas aeruginosa fitness in the presence of imipenem.
abstract: A large number of genes coding for enzymes predicted to synthesize and degrade 3'-5-cyclic diguanylic acid (c-di-GMP) is found in most bacterial genomes and this dinucleotide emerged as an intracellular signal-controlling bacterial behaviour. An association between high levels of c-di-GMP and antibiotic resistance may be expected because c-di-GMP regulates biofilm formation and this mode of growth leads to enhanced antibiotic resistance. However, a clear understanding of this correlation has not been established. We found that increased levels of c-di-GMP in Pseudomonas aeruginosa improve fitness in the presence of imipenem, even when grown as planktonic cells. P. aeruginosa post-transcriptionally regulates the amounts of five porins in response to c-di-GMP, including OprD, responsible for imipenem uptake. Cells with low c-di-GMP levels are consequently more sensitive to this antibiotic. Main efflux pumps or β-lactamase genes did not show altered mRNA levels in P. aeruginosa strains with modified different c-di-GMP concentrations. Together, our findings show that c-di-GMP levels modulate fitness of planktonic cultures in the presence of imipenem.
authors.forename: Gianlucca G
authors.initials: GG
authors.lastname: Nicastro
authors.forename: Gilberto H
authors.initials: GH
authors.lastname: Kaihami
authors.forename: Thays O
authors.initials: TO
authors.lastname: Pereira
authors.forename: Diogo A
authors.initials: DA
authors.lastname: Meireles
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Groleau
authors.forename: Eric
authors.initials: E
authors.lastname: Déziel
authors.forename: Regina L
authors.initials: RL
authors.lastname: Baldini
mesh_terms: D000220:Adaptation, Biological; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism; D015378:Imipenem / Q000494:pharmacology*; D018272:Porins / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D018272:Porins; C062025:bis(3',5')-cyclic diguanylic acid; D015378:Imipenem; D006152:Cyclic GMP