Efflux pump inhibitors reduce the invasiveness of Pseudomonas aeruginosa

• Published in: International journal of antimicrobial agents 2009-10, Vol.34 (4), p.343-346
• Main Authors: Hirakata, Yoichi, Kondo, Akira, Hoshino, Kazuki, Yano, Hisakazu, Arai, Kazuaki, Hirotani, Ayako, Kunishima, Hiroyuki, Yamamoto, Natsuo, Hatta, Masumitsu, Kitagawa, Miho, Kohno, Shigeru, Kaku, Mitsuo
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Bacterial Outer Membrane Proteins - genetics; Bacterial Outer Membrane Proteins - metabolism; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biological and medical sciences; Cell Line; Culture Media; Dipeptides - pharmacology; Drug Resistance, Bacterial; Infectious Disease; Kidney - cytology; Kidney - microbiology; Medical sciences; Membrane Transport Proteins - genetics; Membrane Transport Proteins - metabolism; Microbial Sensitivity Tests - methods; Pharmacology. Drug treatments; Piperidines - pharmacology; Pseudomonas aeruginosa; Pseudomonas aeruginosa - drug effects; Pseudomonas aeruginosa - genetics; Pseudomonas aeruginosa - growth & development; Pseudomonas aeruginosa - pathogenicity; Quaternary Ammonium Compounds - pharmacology
• ISSN: 0924-8579; 1872-7913
• DOI: 10.1016/j.ijantimicag.2009.06.007

Abstract 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-β-naphthylamide (PAβN) 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 PAβN. 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.