Multidrug efflux systems play an important role in the invasiveness of Pseudomonas aeruginosa

Yoichi Hirakata, Ramakrishnan Srikumar, Keith Poole, Naomasa Gotoh, Takashi Suematsu, Shigeru Kohno, Shimeru Kamihira, Robert E.W. Hancock, David P. Speert

Research output: Contribution to journalArticlepeer-review

175 Citations (Scopus)

Abstract

Pseudomonas aeruginosa is an important opportunistic human pathogen. Certain strains can transmigrate across epithelial cells, and their invasive phenotype is correlated with capacity to cause invasive human disease and fatal septicemia in mice. Four multidrug efflux systems have been described in P. aeruginosa, however, their contribution to virulence is unclear. To clarify the role of efflux systems in invasiveness, P. aeruginosa PAO1 wild-type (WT) and its efflux mutants were evaluated in a Madin-Darby canine kidney (MDCK) epithelial cell monolayer system and in a murine model of endogenous septicemia. All efflux mutants except a ΔmexCD-oprJ deletion demonstrated significantly reduced invasiveness compared with WT. In particular, a ΔMexAB-oprM deletion strain was compromised in its capacity to invade or transmigrate across MDCK cells, and could not kill mice, in contrast to WT which was highly invasive (P < 0.0006) and caused fatal infection (P < 0.0001). The other mutants, including ΔmexB and ΔmexXY mutants, were intermediate between WT and the ΔmexAB-oprM mutant in invasiveness and murine virulence. Invasiveness was restored to the ΔmexAB-oprM mutant by complementation with mexAB-oprM or by addition of culture supernatant from MDCK cells infected with WT. We conclude that the P. aeruginosa MexAB-OprM efflux system exports virulence determinants that contribute to bacterial virulence.

Original languageEnglish
Pages (from-to)109-118
Number of pages10
JournalJournal of Experimental Medicine
Volume196
Issue number1
DOIs
Publication statusPublished - 1 Jul 2002
Externally publishedYes

Keywords

  • Bacterial invasion
  • Endogenous bacteremia
  • Multidrug efflux system
  • Outer membrane protein
  • Pseudomonas aeruginosa

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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