d13-9001 and phenylalanine-arginine-beta-naphthylamide

Efflux systems are thought to contribute to antimicrobial resistance in Pseudomonas aeruginosa. The mexAB-oprM deletion strain of P. aeruginosa PAO1 is compromised in its capacity to invade Madin-Darby canine kidney (MDCK) cells, suggesting that P. aeruginosa exports invasion determinants using a MexAB-OprM system. The influences of efflux pump inhibitors (EPIs), including the broad-spectrum EPI Phe-Arg-beta-naphthylamide (PAbetaN) and MexAB-OprM-specific EPI D13-9001, on the invasion of wild-type (WT) P. aeruginosa PAO1 and its MexAB-OprM-overproducing nalB strain were examined. The invasiveness of PAO1 WT and nalB strains was inhibited in the presence of EPIs in a concentration-dependent manner. Reduction of the invasiveness of both strains was greater for D13-9001 compared with PAbetaN. EPIs are thought to be useful in reducing the invasiveness and antimicrobial resistance of P. aeruginosa and thus may be promising as new anti-infectious agents.

Topics: Anti-Bacterial Agents; Bacterial Outer Membrane Proteins; Bacterial Proteins; Cell Line; Culture Media; Dipeptides; Drug Resistance, Bacterial; Kidney; Membrane Transport Proteins; Microbial Sensitivity Tests; Piperidines; Pseudomonas aeruginosa; Quaternary Ammonium Compounds