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.

journal_name

Arch Biochem Biophys

authors

Gardner PR

doi

10.1006/abbi.1996.0390

subject

Has Abstract

pub_date

1996-09-01 00:00:00

pages

267-74

issue

1

eissn

0003-9861

issn

1096-0384

pii

S0003-9861(96)90390-2

journal_volume

333

pub_type

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