Efflux pump inhibitors reduce the invasiveness of Pseudomonas aeruginosa

Yoichi Hirakata; Akira Kondo; Kazuki Hoshino; Hisakazu Yano; Kazuaki Arai; Ayako Hirotani; Hiroyuki Kunishima; Natsuo Yamamoto; Masumitsu Hatta; Miho Kitagawa; Shigeru Kohno; Mitsuo Kaku

doi:10.1016/j.ijantimicag.2009.06.007

Efflux pump inhibitors reduce the invasiveness of Pseudomonas aeruginosa

Int J Antimicrob Agents. 2009 Oct;34(4):343-6. doi: 10.1016/j.ijantimicag.2009.06.007. Epub 2009 Jul 16.

Authors

Yoichi Hirakata¹, Akira Kondo, Kazuki Hoshino, Hisakazu Yano, Kazuaki Arai, Ayako Hirotani, Hiroyuki Kunishima, Natsuo Yamamoto, Masumitsu Hatta, Miho Kitagawa, Shigeru Kohno, Mitsuo Kaku

Affiliation

¹ Department of Infection Control and Laboratory Diagnostics, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai 980-8574, Japan. [email protected]

PMID: 19615866
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-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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / pharmacology*
Bacterial Outer Membrane Proteins / genetics
Bacterial Outer Membrane Proteins / metabolism
Bacterial Proteins / genetics
Bacterial Proteins / metabolism
Cell Line
Culture Media
Dipeptides / pharmacology*
Drug Resistance, Bacterial
Kidney / cytology
Kidney / microbiology
Membrane Transport Proteins / genetics
Membrane Transport Proteins / metabolism
Microbial Sensitivity Tests / methods
Piperidines / pharmacology*
Pseudomonas aeruginosa / drug effects*
Pseudomonas aeruginosa / genetics
Pseudomonas aeruginosa / growth & development
Pseudomonas aeruginosa / pathogenicity*
Quaternary Ammonium Compounds / pharmacology*

Substances

Anti-Bacterial Agents
Bacterial Outer Membrane Proteins
Bacterial Proteins
Culture Media
D13-9001
Dipeptides
Membrane Transport Proteins
MexA protein, Pseudomonas aeruginosa
MexB protein, Pseudomonas aeruginosa
OprM protein, Pseudomonas aeruginosa
Piperidines
Quaternary Ammonium Compounds
phenylalanine arginine beta-naphthylamide