Carbapenem-resistance is a great challenge for antimicrobial therapy in Pseudomonas aeruginosa multidrug-resistant infections, as it reduces therapeutic options. This study investigated carbapenem-resistance mechanisms six strains of non-carbapenemase-producing P. aeruginosa. Minimal inhibitory concentrations imipenem and meropenem were determined by epsilometric test broth microdilution. Mutat...

The metal-specific CzcRS two-component system in Pseudomonas aeruginosa is involved in the repression of the OprD porin, causing in turn carbapenem antibiotic resistance in the presence of high zinc concentration. It has also been shown that CzcR is able to directly regulate the expression of multiple genes including virulence factors. CzcR is therefore an important regulator connecting (i) met...

Pseudomonas aeruginosa strains that overexpress mexCD-oprJ become hypersusceptible to imipenem. Disruption of AmpC induction has been suggested to cause this phenotype. However, data from this study demonstrate that hypersusceptibility to imipenem can develop without changes in ampC expression or AmpC activity. Furthermore, hypersusceptibility is not caused by changes in expression of the outer...

Carbapenems are major antibiotics reserved to human medicine. This study aimed to investigate the mechanisms of carbapenem resistance of a selection of Pseudomonas aeruginosa veterinary strains from the French network Resapath. Thirty (5.7%) imipenem and/or meropenem non-susceptible P. aeruginosa of canine (n = 24), feline (n = 5), or bovine (n = 1) origin were identified in a large collection ...

The Pseudomonas aeruginosa outer membrane is intrinsically impermeable to many classes of antibiotics, due in part to its relative lack of general uptake pathways. Instead, this organism relies on a large number of substrate-specific uptake porins. Included in this group are the 19 members of the OprD family, which are involved in the uptake of a diverse array of metabolites. One of these porin...

Pseudomonas aeruginosa OprD is a specific porin which facilitates the uptake of basic amino acids and imipenem across the outer membrane. In this study, we examined the effects of deletions in six of the proposed eight surface loops of OprD on the in vivo and in vitro functions of this protein. Native OprD formed very small channels in planar lipid bilayers, with an average single-channel condu...

Pseudomonas aeruginosa is a prevalent nosocomial pathogen (1) and a threat in neonatal and intensive care units, causing deadly infections in ventilator-associated pneumonia or immunosuppressed patients. P. aeruginosa strains causing these infections are frequently multiresistant, and treatment is a nightmare for clinicians (2). P. aeruginosa colonizing the lungs of cystic fibrosis patients can...

The objective of this study is to identify the structural features governing the transport of molecules through nanometric channel proteins at a molecular level. Our focus is to come up with a precise understanding of the structure and dynamics of the outer membrane porin OprD of the Gram-negative bacterium Pseudomonas aeruginosa by studying the translocation of natural amino acid residues/subs...