Efflux pump inhibitors reduce the invasiveness of Pseudomonas aeruginosa.
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.
Hirakata
Yoichi
Y
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
Kondo
Akira
A
Hoshino
Kazuki
K
Yano
Hisakazu
H
Arai
Kazuaki
K
Hirotani
Ayako
A
Kunishima
Hiroyuki
H
Yamamoto
Natsuo
N
Hatta
Masumitsu
M
Kitagawa
Miho
M
Kohno
Shigeru
S
Kaku
Mitsuo
M
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*
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