Inactivation of a Pseudomonas aeruginosa quorum-sensing signal by human airway epithelia

  1. Carlene K. Chun*,,,
  2. Egon A. Ozer,§,,
  3. Michael J. Welsh§,,
  4. Joseph Zabner§, and
  5. E. P. Greenberg,**,††
  1. *Pacific Biomedical Research Center, Kewalo Marine Laboratory, 41 Ahui Street, University of Hawaii, Honolulu, HI 96813; and §Department of Internal Medicine, Molecular Biology Graduate Program, **Department of Microbiology, Howard Hughes Medical Institute, and W. M. Keck Microbial Communities and Cell Signaling Program, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242
  1. Contributed by Michael J. Welsh, December 31, 2003

Abstract

Mammalian airways protect themselves from bacterial infection by using multiple defense mechanisms including antimicrobial peptides, mucociliary clearance, and phagocytic cells. We asked whether airways might also target a key bacterial cell-cell communication system, quorum-sensing. The opportunistic pathogen Pseudomonas aeruginosa uses two quorum-sensing molecules, N-(3-oxododecanoyl)-l-homoserine lactone (3OC12-HSL) and N-butanoyl-l-homoserine lactone (C4-HSL), to control production of extracellular virulence factors and biofilm formation. We found that differentiated human airway epithelia inactivated 3OC12-HSL. Inactivation was selective for acyl-HSLs with certain acyl side chains, and C4-HSL was not inactivated. In addition, the capacity for inactivation varied widely in different cell types. 3OC12-HSL was inactivated by a cell-associated activity rather than a secreted factor. These data suggest that the ability of human airway epithelia to inactivate quorum-sensing signal molecules could play a role in the innate defense against bacterial infection.

Footnotes

  • †† To whom correspondence should be addressed at: Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242. E-mail: everett-greenberg{at}uiowa.edu.

  • C.K.C. and E.A.O. contributed equally to this work.

  • Abbreviations: CHO, Chinese hamster ovary; EMEM, Eagle's minimal essential medium; HSL, homoserine lactone.

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