title: Efflux pump inhibitors reduce the invasiveness of Pseudomonas aeruginosa.
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-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.
authors.affiliation: Department of Infection Control and Laboratory Diagnostics, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai 980-8574, Japan. hiraichi@mail.tains.tohoku.ac.jp
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Hirakata
authors.forename: Akira
authors.initials: A
authors.lastname: Kondo
authors.forename: Kazuki
authors.initials: K
authors.lastname: Hoshino
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Yano
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Arai
authors.forename: Ayako
authors.initials: A
authors.lastname: Hirotani
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kunishima
authors.forename: Natsuo
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Masumitsu
authors.initials: M
authors.lastname: Hatta
authors.forename: Miho
authors.initials: M
authors.lastname: Kitagawa
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Kaku
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D003470:Culture Media; D004151:Dipeptides / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D007668:Kidney / Q000166:cytology / Q000382:microbiology; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D008826:Microbial Sensitivity Tests / Q000379:methods; D010880:Piperidines / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D003470:Culture Media; C525716:D13-9001; D004151:Dipeptides; D026901:Membrane Transport Proteins; C118598:MexA protein, Pseudomonas aeruginosa; C118597:MexB protein, Pseudomonas aeruginosa; C402263:OprM protein, Pseudomonas aeruginosa; D010880:Piperidines; D000644:Quaternary Ammonium Compounds; C419365:phenylalanine arginine beta-naphthylamide