Advertisement

Antonie van Leeuwenhoek

, Volume 58, Issue 2, pp 107–114 | Cite as

Inhibition and killing of fungi by the polyamine oxidase-polyamine system

Antifungal activity of the PAO-polyamine system
  • Stuart M. Levitz
  • David J. DiBenedetto
  • Richard D. Diamond
Article

Abstract

Both components of the polyamine oxidase (PAO)-polyamine system are known to be present in phagocytes and have thus been postulated to contribute to the antimicrobial activity of these cells. Therefore, the effects of the PAO-polyamine system on three medically important opportunistic fungi were examined. Yeasts of Cryptococcus neoformans, but not Candida albicans blastoconidia or Aspergillus fumigatus conidia, were efficiently killed by the system. Two putative end products of the system, hydrogen peroxide and acrolein, both killed C. neoformans at concentrations attainable with the whole system. However, catalase failed to inhibit activity of the whole system, making hydrogen peroxide an unlikely mediator of killing. Although C. albicans blastoconidia and A. fumigatus conidia were not killed by the PAO-polyamine system, germ tube formation by the former, and hyphal growth by the latter, were markedly inhibited. These data establish that the PAO-polyamine system possesses antifungal activity.

Key words

Aspergillus fumigatus Candida albicans Cryptococcus neoformans fungi polyamine polyamine oxidase 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Alarcon RA (1970) Acrolein: IV. Evidence for the formation of the cytotoxic aldehyde acrolein from anzymatically oxidized spermine or spermidine. Arch. Biochem. and Biophys. 137: 365–72.Google Scholar
  2. Brummer E & Stevens DA (1987) Fungicidal mechanisms of activated macrophages: Evidence for nonoxidative mechanisms for killing of Blastomyces dermatitidis. Infect. Immun. 55: 3221–4Google Scholar
  3. Brummer E, Morrison CJ & Stevens DA (1985) Recombinant and natural gamma-interferon activation of macrophages in vitro: Different dose requirements for induction of killing activity against phagocytizable and nonphagocytizable fungi. Infect. Immun. 49: 724–30Google Scholar
  4. Cohen IR & Altshuller AP (1961) A new spectrophotometric method for the determination of acrolein in combustion gases and in the atmosphere. Analytical Chemistry 33: 726–733Google Scholar
  5. Cohen LF, Lundgren DW & Farrell PM (1976) Distribution of spermidine and spermine in blood from cystic fibrosis patients and control subjects. Blood 48: 469–75Google Scholar
  6. Cooper KD, Shukla JB & Rennert OM (1976) Polyamine distribution in cellular compartments of blood and in aging erythrocytes. Clin. Chim. Acta 73: 71–88Google Scholar
  7. Elsbach P & Weiss J (1983) A reevaluation of the roles of the O2-dependent and O2-independent microbicidal systems of phagocytes. Rev. Infect. Dis. 5: 843–53Google Scholar
  8. Ferrante A, Ljungstrom I, Rzepczyk CM & Morgan DML (1986) Differences in sensitivity of Schistosoma mansoni schistosomula, Dirofilaria immitis microfilariae, and Nematospiroides dubius third-stage larvae to damage by the polyamine oxidase-polyamine system. Infect. Immun. 53: 606–10Google Scholar
  9. Ferrante A, Rzepczyk CM & Saul AJ (1984) Polyamine oxidase-mediated trypanosome killing: The role of hydrogen peroxide and aldehydes. J. Immunol. 133: 2157–62Google Scholar
  10. Fromtling RA & Shadomy HJ (1986) An overview of macrophage-fungal interactions. Mycopathol. 93: 77–93Google Scholar
  11. Gahl WA & Pitot HC (1982) Polyamine degradation in foetal and adult bovine serum. Biochem. J. 202: 603–11Google Scholar
  12. Granger DL, Perfect JR & Durack DT (1986) Macrophage-mediated fungistasis in vitro: Requirements for intracellular and extracellular cytotoxicity. J. Immunol. 136: 672–80Google Scholar
  13. Heby O (1981) Role of polyamines in the control of cell proliferation and differentiation. Differentiation 19: 1–20Google Scholar
  14. Kierszenbaum F, Wirth JJ, McCann PP & Sjoerdsma A (1987) Impairment of macrophage function by inhibitors of ornithine decarboxylase activity. Infect. Immun 55: 2461–4Google Scholar
  15. Levitz SM (1989) Aspergillosis In: Saunders WB (Ed) Philadelphia, PA. Infectious Disease Clinics of North America 3: 1–18Google Scholar
  16. Levitz SM & Diamond RD (1984) Killing of Aspergillus fumigatus spores and Candida albicans yeast phase by the ironhydrogen peroxide-iodide cytotoxic system: Comparison with the myeloperoxidase-hydrogen peroxide-halide system. Infect. Immun. 43: 1100–2Google Scholar
  17. Levitz SM & Diamond RD (1985) Mechanisms of resistance of Aspergillus fumigatus conidia to killing by neutrophils in vitro. J. Infect. Dis. 152: 33–42Google Scholar
  18. Levitz SM & DiBenedetto DJ (1988) Differential stimulation of murine resident peritoneal cells by selectively opsonized encapsulated and acapsular Cryptococcus neoformans. Infect. Immun. 56: 2544–51Google Scholar
  19. Levitz SM & DiBenedetto DJ (1989) Paradoxical role of capsule in murine bronchoalveolar macrophage-mediated killing of Cryptococcus neoformans. J. Immunol. 142: 659–665Google Scholar
  20. Morgan DML (1980) Polyamine Oxidases. In: Gaugas JM (Ed) Polyamines in Biomedical Research (pp 285–302). Wiley, Chichester, N.Y.Google Scholar
  21. Morgan DML (1985) Polyamine oxidases. Biochem. Soc. Trans. 13: 322–5Google Scholar
  22. Morgan DML, Ferulga J & Allison AC (1980) Polyamine Oxidase and Macrophage Function. In: Gaugas JM (Ed), Polyamines in Biomedical Research (pp 303–8) Wiley, Chichester, N.Y.Google Scholar
  23. Oppenheim FG, Xu T, McMillian FM, Levitz SM, Diamond RD, Offner GD & Troxler RF (1988) Histatins, a novel family of histidine-rich proteins in human parotid secretion. J. Biol. Chem. 263: 7472–7Google Scholar
  24. Patterson-Delafield J, Martinez RJ & Lehrer RI (1980) Microbicidal cationic proteins in rabbit alveolar macrophages: a potential host defence mechanism. Infect. Immun. 30: 180–92Google Scholar
  25. Ruch W, Cooper PH & Baggiolini M (1983) Assay of H2O2 production by macrophages and neutrophils with homovanillic acid and horse-radish peroxidase. J. Immunol. Methods 63: 347–57Google Scholar
  26. Rzepczyk CM, Saul AJ & Ferrante A (1984) Polyamine oxidase-mediated intraerythrocytic killing of Plasmodium falciparum: Evidence against the role of reactive oxygen metabolites. Infect. Immun. 43: 238–44Google Scholar
  27. Waldorf AR, Levitz SM & Diamond RD (1984) In vivo bronchoalveolar macrophage defence against Rhizopus oryzae and Aspergillus fumigatus. J. Infect. Dis. 150: 752–60Google Scholar
  28. Wu-Hsieh BA & Howard DH (1987) Inhibition of the intracellular growth of Histoplasma capsulatum by recombinant murine gamma interferon. Infect. Immun. 55: 1014–16Google Scholar

Copyright information

© Kluwer Academic Publishers 1990

Authors and Affiliations

  • Stuart M. Levitz
    • 1
    • 2
  • David J. DiBenedetto
    • 1
    • 2
  • Richard D. Diamond
    • 1
    • 2
  1. 1.Evans Memorial Department of Clinical ResearchThe University Hospital, Boston University Medical CenterBostonUSA
  2. 2.the Department of MedicineThe University Hospital, Boston University Medical CenterBostonUSA

Personalised recommendations