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 Citations (Scopus)

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

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Epoxide Hydrolases
Hydrolases
Epoxy Compounds
Virulence Factors
Pathogens
Hydrolysis
Proteins
Molecules
Ions
Ion Channels

Keywords

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

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis

Cite this

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

Inhibiting an Epoxide Hydrolase Virulence Factor from Pseudomonas aeruginosa Protects CFTR. / Bahl, Christopher D.; Hvorecny, Kelli L.; Bomberger, Jennifer M.; Stanton, Bruce A.; Hammock, Bruce D.; Morisseau, Christophe; Madden, Dean R.

In: Angewandte Chemie - International Edition, Vol. 54, No. 34, 01.08.2015, p. 9881-9885.

Research output: Contribution to journalArticle

Bahl, CD, Hvorecny, KL, Bomberger, JM, Stanton, BA, Hammock, BD, Morisseau, C & Madden, DR 2015, 'Inhibiting an Epoxide Hydrolase Virulence Factor from Pseudomonas aeruginosa Protects CFTR', Angewandte Chemie - International Edition, vol. 54, no. 34, pp. 9881-9885. https://doi.org/10.1002/anie.201503983
Bahl, Christopher D. ; Hvorecny, Kelli L. ; Bomberger, Jennifer M. ; Stanton, Bruce A. ; Hammock, Bruce D. ; Morisseau, Christophe ; Madden, Dean R. / Inhibiting an Epoxide Hydrolase Virulence Factor from Pseudomonas aeruginosa Protects CFTR. In: Angewandte Chemie - International Edition. 2015 ; Vol. 54, No. 34. pp. 9881-9885.
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