Cyclic-di-GMP levels affect Pseudomonas aeruginosa fitness in the presence of imipenem

Gianlucca G Nicastro (1) , Gilberto Hideo Kaihami (1) , Thays O Pereira (1) , Diogo A Meireles (1) , Marie-Christine Groleau (2) , Eric Déziel (2) , Regina L Baldini (1)

1 Departamento de Bioquímica, Instituto de Química
2 INRS-IAF - Institut Armand Frappier

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 intra-cellular 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.

Domaines: Microbiologie et Parasitologie; Ecologie, Environnement

Gianlucca G Nicastro, Gilberto Hideo Kaihami, Thays O Pereira, Diogo A Meireles, Marie-Christine Groleau, et al.. Cyclic-di-GMP levels affect Pseudomonas aeruginosa fitness in the presence of imipenem. Environmental Microbiology, 2014, 16 (5), pp.1321-1333. ⟨10.1111/1462-2920.12422⟩. ⟨hal-01178794⟩