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The Penicillium chrysogenum-derived antifungal peptide shows no toxic effects on mammalian cells in the intended therapeutic concentration

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Abstract

Certain filamentous fungi, such as the penicillin-producing strain Penicillium chrysogenum, secrete small, highly basic and cysteine-rich proteins with antifungal effects. Affected fungi include a number of important zoopathogens, including those infecting humans. Recent studies, however, have pointed to a membrane-perturbing effect of these antifungal compounds, apparent as a potassium efflux from affected fungal cells. If present on mammalian cells, this would severely hinder the potential therapeutic use of these molecules. Here we studied the effects of the P. chrysogenum-derived antifungal peptide (PAF) on a number of mammalian cells to establish whether the protein has any cytotoxic effects, alters transmembrane currents on excitable cells or activates the immune system. PAF, in a concentration range of 2–100 μg/ml, did not cause any cytotoxicity on human endothelial cells from the umbilical vein. Applied at 10 μg/ml, it also failed to modify voltage-gated potassium channels of neurones, skeletal muscle fibers, and astrocytes. PAF also left the hyperpolarization-activated non-specific cationic current (Ih) and the L-type calcium current unaffected. Finally, up to 2 μg/ml, PAF did not induce the production of pro-inflammatory cytokines such as IL-6, IL-8, and TNF-α. These results suggest that PAF should have only minor, if any, effects on mammalian cells in the intended therapeutic concentration range.

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Acknowledgements

The authors wish to thank R. Öri and I. Varga for their technical assistance. The work was supported by research grants from OTKA (TS040773, T034894, T046067, T034315, and T037473) and the Office for Higher Education Programs (0092/2001) of Hungary. I.P. is a recipient of the Széchenyi István Scholarship. F.M. was supported by the Austrian Science Foundation (FWF grant P-15261) and the University of Innsbruck (grant X8).

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Authors and Affiliations

  1. Department of Physiology, RCMM, MHSC, University of Debrecen, P.O. Box 22, Debrecen, Hungary, 4012

    Henrietta Szappanos, Gyula Péter Szigeti, Balázs Pál, Zoltán Rusznák & Géza Szűcs

  2. Department of Immunology, RCMM, MHSC, University of Debrecen, P.O. Box 22, Debrecen, Hungary, 4012

    Éva Rajnavölgyi

  3. Department of Medicine, MHSC, University of Debrecen, P.O. Box 22, Debrecen, Hungary, 4012

    József Balla

  4. Department of Neonatology, MHSC, University of Debrecen, P.O. Box 22, Debrecen, Hungary, 4012

    György Balla & Emőke Nagy

  5. Department of Microbiology and Biotechnology, Faculty of Sciences, University of Debrecen, P.O. Box 22, Debrecen, Hungary, 4012

    Éva Leiter & István Pócsi

  6. Department of Molecular Biology, Medical University of Innsbruck, Innsbruck, Austria

    Florentine Marx

  7. Cell Physiology Research Group of the Hungarian Academy of Sciences, University of Debrecen, P.O. Box 22, Debrecen, Hungary, 4012

    László Csernoch

  8. Department of Physiology, Medical and Health Science Center, University of Debrecen, P.O. Box 22, Debrecen, Hungary, 4012

    László Csernoch

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  1. Henrietta Szappanos
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  2. Gyula Péter Szigeti
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  3. Balázs Pál
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  4. Zoltán Rusznák
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  5. Géza Szűcs
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  6. Éva Rajnavölgyi
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  7. József Balla
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  8. György Balla
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  9. Emőke Nagy
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  10. Éva Leiter
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  11. István Pócsi
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  12. Florentine Marx
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  13. László Csernoch
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Correspondence to László Csernoch.

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Szappanos, H., Szigeti, G.P., Pál, B. et al. The Penicillium chrysogenum-derived antifungal peptide shows no toxic effects on mammalian cells in the intended therapeutic concentration. Naunyn-Schmiedeberg's Arch Pharmacol 371, 122–132 (2005). https://doi.org/10.1007/s00210-004-1013-7

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  • DOI: https://doi.org/10.1007/s00210-004-1013-7

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