title: Superoxide production by the mycobacterial and pseudomonad quinoid pigments phthiocol and pyocyanine in human lung cells.
abstract: The quinoid pigments pthiocol, produced by Mycobacterium tuberculosis, and pyocyanine, produced by Pseudomonas aeruginosa, were examined for their effects on O2.- production in cultured human lung epithelial-like A549 cells. Intracellular O2.- levels were measured using the O2.-sensitive aconitase(s), and rates of O2.- generation were assessed from rates of antimycin-resistant respiration. Elevated O2.- was detected in cells exposed to < 25 microM phthiocol and < 2 microM pyocyanine in neutral pH medium, and both agents impaired cell growth. The O2.- scavenging manganoporphyrin, Mn(III)TMPyP, partially protected cells against pyocyanine and phthiocol-mediated growth inhibition. O2.- production by phthiocol and pyocyanine was enhanced by acidification of the growth medium. Surprisingly, the dicumarol-inhibitable quinoid detoxification enzyme DT-diaphorase was a significant source of phthiocol and pyocyanine-mediated O2.- generation in cells. O2.- production in macrophages by the phthiocol analog, menadione, was shown to impair macrophage mitochondrial respiration and bactericidal activity toward Escherichia coli. Phthiocol and pyocyanine, by producing O2.-/H2O2, and inhibiting host cell aconitase activity, energetics, and other host cell functions, may contribute to the pathogenicity of M. tuberculosis and P. aeruginosa.
authors.affiliation: Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206, USA.
authors.forename: P R
authors.initials: PR
authors.lastname: Gardner
mesh_terms: D000154:Aconitate Hydratase / Q000378:metabolism; D000968:Antimycin A / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D001728:Dicumarol / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008168:Lung; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008665:Metalloporphyrins / Q000494:pharmacology; D009169:Mycobacterium tuberculosis / Q000737:chemistry; D009285:Naphthoquinones / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D010860:Pigments, Biological / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000737:chemistry; D011710:Pyocyanine / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism*; D014812:Vitamin K / Q000494:pharmacology
chemical_list: D016166:Free Radical Scavengers; D008665:Metalloporphyrins; D009285:Naphthoquinones; D010860:Pigments, Biological; D013481:Superoxides; D014812:Vitamin K; D000968:Antimycin A; C050950:tetrakis(N-methyl-4-pyridiniumyl)porphine manganese(III) complex; D001728:Dicumarol; C008902:phthiocol; D011710:Pyocyanine; D000154:Aconitate Hydratase