Outer membrane permeability of Pseudomonas aeruginosa through β-lactams: new evidence on the role of OprD and OpdP porins in antibiotic resistance.

Abstract

Gram-negative bacteria are a major concern for public health, particularly due to the continuous rise of antibiotic resistance. A major factor that helps the development of resistance is the outer membrane that is essential since it acts as a strong permeability barrier to many antibiotics that are effective against other bacteria. In this study, we determine the specific permeability coefficients for various antibiotics in Pseudomonas aeruginosa strains, which differ from each other for their porin expressions. We showed that OprD and OpdP porins contribute both to internalize meropenem and biapenem. Using qRT-PCR, we demonstrated that their expression is dependent of the various phases of cellular growth. We were able to show how the OpdP porin is less expressed in exponential growth phases, while it tends to be produced when the bacterial culture enters into the latent phase, in an inversely proportional way compared to the OprD porin. The deletion of the OpdP porin, in the presence of meropenem at concentrations equivalent to the MIC values, contributes to the selection of carbapenem-resistant strains. Therefore, the presence of mutations/deletions of the OpdP porin should receive greater consideration from a clinical point of view as the use of meropenem at nonoptimal concentrations could lead to the appearance of resistance phenotypes.IMPORTANCECarbapenem-resistant strains of Pseudomonas aeruginosa are among the major threats to public health. The permeability of the outer membrane for the β-lactam antibiotics is one of the major factors that reduce the activity of the antibiotics. In this study, we measure the low permeability coefficient of the P. aeruginosa outer membrane to β-lactams. The methodology we develop to determine the permeability can be applied to other antibiotic families and/or pathogens.