Inhibiting an Epoxide Hydrolase Virulence Factor from Pseudomonas aeruginosa Protects CFTR

Christopher D. Bahl, Kelli L. Hvorecny, Jennifer M. Bomberger, Bruce A. Stanton, Bruce D. Hammock, Christophe Morisseau, Dean R. Madden

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Opportunistic pathogens exploit diverse strategies to sabotage host defenses. Pseudomonas aeruginosa secretes the CFTR inhibitory factor Cif and thus triggers loss of CFTR, an ion channel required for airway mucociliary defense. However, the mechanism of action of Cif has remained unclear. It catalyzes epoxide hydrolysis, but there is no known role for natural epoxides in CFTR regulation. It was demonstrated that the hydrolase activity of Cif is strictly required for its effects on CFTR. A small-molecule inhibitor that protects this key component of the mucociliary defense system was also uncovered. These results provide a basis for targeting the distinctive virulence chemistry of Cif and suggest an unanticipated role of physiological epoxides in intracellular protein trafficking.

Original languageEnglish (US)
Pages (from-to)9881-9885
Number of pages5
JournalAngewandte Chemie - International Edition
Volume54
Issue number34
DOIs
StatePublished - Aug 1 2015

Keywords

  • CFTR
  • epoxide hydrolase
  • inhibitors
  • Pseudomonas aeruginosa
  • virulence factors

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis

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    Bahl, C. D., Hvorecny, K. L., Bomberger, J. M., Stanton, B. A., Hammock, B. D., Morisseau, C., & Madden, D. R. (2015). Inhibiting an Epoxide Hydrolase Virulence Factor from Pseudomonas aeruginosa Protects CFTR. Angewandte Chemie - International Edition, 54(34), 9881-9885. https://doi.org/10.1002/anie.201503983