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The Pseudomonas aeruginosa virulence factor Cif inhibits the generation of the pro‐resolving lipid mediator 15‐epi lipoxin A 4
Author(s) -
Bomberger Jennifer,
Flitter Becca,
Ono Emiko,
Hvorecny Kelli,
Bahl Christopher,
Madden Dean,
Levy Bruce
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.672.2
Subject(s) - pseudomonas aeruginosa , virulence factor , lipoxin , chemistry , inflammation , microbiology and biotechnology , epoxide hydrolase , virulence , cystic fibrosis , mutant , biology , biochemistry , in vitro , bacteria , immunology , gene , microsome , genetics
Pseudomonas aeruginosa is an opportunistic Gram‐negative bacteria that causes a wide range of severe nosocomial infections, especially in immunocompromised patients with chronic inflammatory lung disease. P. aeruginosa infections are characterized by persistent and robust neutrophilic inflammation which can cause damage to host tissue. Lipoxins, including 15‐epi‐lipoxin A 4 (15‐epi‐LXA 4 ), are lipid mediators that play a critical role in resolving inflammation and promoting tissue homeostasis.The production of 14,15‐epoxy‐eicosatrienoic acid (14,15‐EET) by airway epithelial cells stimulates the generation of 15‐epi‐LXA 4 by neighboring neutrophils through transcellular biosynthesis. We have identified a P. aeruginosa virulence factor with epoxide hydrolase activity called cystic fibrosis inhibitory factor (Cif), which we hypothesize disrupts the generation of 15‐epi‐LXA 4 . We show that both P. aeruginosa and recombinant Cif protein alone hydrolyzes the epoxide moiety of (14,15‐EET), whereas a cif deletion mutant P. aeruginosa or catalytically‐dead D129S mutant of Cif have no effect. Furthermore, the Cif‐mediated reduction of 14,15‐EET inhibited the generation of 15‐epi‐LXA 4 by activated neutrophils in vitro . The D129S mutant Cif was also incapable of reducing 15‐epi‐LXA 4 biosynthesis.Taken together, our data suggest a novel model whereby the P. aeruginosa virulence factor Cif reduces 15‐epi‐LXA 4 in the airways, thus promoting persistent inflammation and consequent lung damage.