Inhibition of Myeloperoxidase by Phenazine‐Based Bacterial Metabolites: Implications for Cystic Fibrosis

Abstract

Cystic fibrosis (CF) patients have chronic airway inflammation due to persistent neutrophil influx in response to bacterial infection, most notably Pseudomonas aeruginosa (PA). Neutrophils express myeloperoxidase (MPO), an enzyme that catalyzes the formation of hypochlorous acid to kill bacteria in the lungs of CF patients. Pyocyanin (PYO) and 1‐hydroxyphenazine (1‐HP) are metabolites abundantly produced by PA, known to cause detrimental effects in the lung; however, the effect of PYO and 1‐HP on MPO activity is not known. We hypothesized that PA produce PYO and 1‐HP as a means of inhibiting MPO and incapacitating this important mammalian host defense mechanism. In order to test this hypothesis, we utilized colorimetric assays of MPO activity in the presence or absence of 1‐HP or PYO. Our data indicate that 1‐HP and PYO inhibit both the peroxidase and chlorination activities of MPO. The data suggest that 1‐HP and PYO can modulate MPO activity and presumably decreasing its antibactericidal functions, and thus acting as a mechanism by which PA can thrive in the CF airway. Identifying the effects PYO and 1‐HP have on MPO will influence overall strategies for therapeutic treatments in cystic fibrosis.