Redox warfare between airway epithelial cells and Pseudomonas: dual oxidase versus pyocyanin

Abstract

The importance of reactive oxygen species-dependent microbial killing by the phagocytic cell NADPH oxidase has been appreciated for some time, although only recently has an appreciation developed for the partnership of lactoperoxidase with related dual oxidases (Duox) within secretions of the airway surface layer. This system produces mild oxidants designed for extracellular killing that are effective against several airway pathogens, including Staphylococcus aureus, Burkholderia cepacia, and Pseudomonas aeruginosa. Establishment of chronic pseudomonas infections involves adaptations to resist oxidant-dependent killing by expression of a redox-active virulence factor, pyocyanin, that competitively inhibits epithelial Duox activity by consuming intracellular NADPH and producing superoxide, thereby inflicting oxidative stress on the host.

Fig.1. The oxidative antimicrobial Duox/SCN-/LPO-system of major airways and counteroffensive mechanisms of Pseudomonas aeruginosa imposed by the redox active virulence factor pyocyanin

A) Lactopreoxidase is produced in the submucosal glands of the airways and accumulates in the airway surface layer, where it converts thiocyanate into microbicidal hypothiocanite using Duox-derived hydrogen peroxide. B) The redox-active Pseudomonas pigment, pyocyanin, enters airway cells, inhibits Duox activity by competing for its substrate (NADPH), and by inhibiting Duox expression. The airway peroxidases, lactoperoxidase (LPO) and myeloperoxidase (MPO), can detoxify pyocyanin using Duox-derived hydrogen peroxide. (Adapted from refs. and 47)