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: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil.
authors: Gianlucca G
authors: GG
authors: Nicastro
authors: Gilberto H
authors: GH
authors: Kaihami
authors: Thays O
authors: TO
authors: Pereira
authors: Diogo A
authors: DA
authors: Meireles
authors: Marie-Christine
authors: MC
authors: Groleau
authors: Eric
authors: E
authors: Déziel
authors: Regina L
authors: RL
authors: Baldini
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D056084:Genetic Fitness / Q000187:drug effects*; D015378:Imipenem / Q000494:pharmacology*; D058977:Molecular Sequence Annotation; D010933:Plankton / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D018272:Porins / Q000235:genetics / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D018272:Porins; C077157:OprD protein, Pseudomonas aeruginosa; C062025:bis(3',5')-cyclic diguanylic acid; D015378:Imipenem; D001618:beta-Lactamases; D006152:Cyclic GMP