Superoxide production by the mycobacterial and pseudomonad quinoid pigments phthiocol and pyocyanine in human lung cells

Arch Biochem Biophys. 1996 Sep 1;333(1):267-74. doi: 10.1006/abbi.1996.0390.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aconitate Hydratase / metabolism
  • Antimycin A / pharmacology
  • Cell Division / drug effects
  • Cell Line
  • Dicumarol / pharmacology
  • Free Radical Scavengers / pharmacology
  • Humans
  • Hydrogen-Ion Concentration
  • Lung
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Metalloporphyrins / pharmacology
  • Mycobacterium tuberculosis / chemistry
  • Naphthoquinones / pharmacology*
  • Oxygen Consumption / drug effects
  • Pigments, Biological / pharmacology*
  • Pseudomonas aeruginosa / chemistry
  • Pyocyanine / pharmacology*
  • Superoxides / metabolism*
  • Vitamin K / pharmacology


  • Free Radical Scavengers
  • Metalloporphyrins
  • Naphthoquinones
  • Pigments, Biological
  • Superoxides
  • Vitamin K
  • Antimycin A
  • tetrakis(N-methyl-4-pyridiniumyl)porphine manganese(III) complex
  • Dicumarol
  • phthiocol
  • Pyocyanine
  • Aconitate Hydratase