Is there a Role for Sterols and Steroids in Fungal Growth and Transition from Yeast to Hyphal-Form and Vice Versa? An Overview

  • Hugo Vanden Bossche
  • Patrick Marichal
Chapter

Abstract

Ergosterol seems to be not only the best-suited sterol to maintain fungal membrane integrity and activity; there is evidence that this 24-alkylated sterol is also involved in critical non-membrane associated functions. A number of fungal species contain steroid-binding proteins and vertebrate steroid hormones seem to affect fungal morphogenesis. In this article it is speculated that ergosterol may also play a role in the yeast-to-mycelium transformation. The possible role of steroid hormones and endogenous ligands in fungal growth and morphogenesis is also discussed.

Keywords

Candida Albicans Sterol Composition Ergosterol Content Ergosterol Biosynthesis Hypha Formation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    W. Köller, Antifungal agents with target sites in sterol functions and biosynthesis, in: “Target Sites of Fungicide Action”, W. Köller, ed., CRC Press, Boca Raton (1992).Google Scholar
  2. 2.
    D.T. Hart, .W.J. Lauwers, G. Willemsens, H. Vanden Bossche and F.R. Opperdoes, Perturbation of sterol biosynthesis by itraconazole and ketoconazole in Leishmania mexicana mexicana infected macrophages, Mol. Biochem. Parasitol. 33: 123 (1989).PubMedCrossRefGoogle Scholar
  3. 3.
    P.Z. Margalith, “Steroid Microbiology”, Charles C. Thomas, Springfield (1986).Google Scholar
  4. 4.
    H. Vanden Bossche, Mode of action of pyridine, pyrimidine and azole antifungals, in: “Sterol Biosynthesis Inhibitors -Pharmaceutical and Agrochemical Aspects”, D. Berg and M. Plempel, eds., Ellis Horwood Ltd., Chichester (1988).Google Scholar
  5. 5.
    H. Vanden Bossche, Importance and role of sterols in fungal membranes, in: “Biochemistry of Cell Walls and Membranes in Fungi”, P.J. Kuhn, A.P.J. Trinci, M.J. Jung, M.W. Goosey and L.G. Copping, eds., Springer-Verlag, Berlin (1990).Google Scholar
  6. 6.
    M.A. Gealt, A. Abdollahi and J.L. Evans, Lipids and lipoidal mycotoxins of fungi, in: “Current Topics in Medical Mycology”, Vol. 3, M.R. McGinnis and M. Borgers, eds., Springer Verlag, New York (1989).Google Scholar
  7. 7.
    P. Mishra and R. Prasad, An overview of lipids of Candida albicans, Prog. Lipid Res. 29: 65 (1990).PubMedCrossRefGoogle Scholar
  8. 8.
    P. Mishra, J. Bolard and R. Prasad, Emerging role of lipids of Candida albicans ,a pathogenic dimorphic yeast, Biochim. Biophys. Ada 1127: 1 (1992).CrossRefGoogle Scholar
  9. 9.
    S.R. Parker and W.D. Nes, Regulation of sterol biosynthesis and its phylogenetic implications, in: “Regulation of Isopentenoid Metabolism”, W.D. Nes, E.J. Parish and J.M. Trzaskos, eds., American Chemical Society, Washington DC (1992).Google Scholar
  10. 10.
    R.D. Cannon and D. Kerridge, Correlation between the sterol composition of membranes and morphology in Candida albicans, J. Med. Vet. Mycol. 26: 57 (1988).Google Scholar
  11. 11.
    S. Sadamori, Comparative study of lipid composition of Candida albicans in the yeast and mycelial forms, Hiroshima J. Med. Sci. 36: 53 (1987).PubMedGoogle Scholar
  12. 12.
    H. Vanden Bossche, P. Marichal, G. Willemsens, D. Bellens, J. Gorrens, I. Roels, M.-C. Coene, L. Le Jeune and P.A.J. Janssen, Saperconazole: a selelective inhibitor of the cytochrome P-450-dependent ergosterol synthesis in Candida albicans, Aspergillus fumigatus and Trichophyton mentagrophytes, Mycoses 33: 335 (1990).Google Scholar
  13. 13.
    C. Arnezeder and W.A. Hampel, Influence of growth rate on the accumulation of ergosterol in yeast-cells in a phosphate limited continuous culture, Biotechn. Lett. 13: 97 (1991).CrossRefGoogle Scholar
  14. 14.
    O. Shimokawa, Y. Kato and H. Nakayawa, Accumulation of 14-methyl sterols and defective hyphal growth in Candida albicans, J. Med. Vet. Mycol 24: 327 (1986).PubMedCrossRefGoogle Scholar
  15. 15.
    P. Marichal, H. Vanden Bossche, H. Moereels and R. Brasseur, Mode of insertion of azole antifungals and sterols in membranes, in: “Molecular Desscription of Biological Membranes by Computer Aided Conformational Analysis”, Vol. 2, R. Brasseur, ed., CRC Press, Boca Raton (1990).Google Scholar
  16. 16.
    M. Bard, N.D. Lees, R.J. Barbuch and D. Sanglard, Characterization of a cytochrome P450 deficient mutant of Candida albicans, Biochem. Biophys. Res. Commun. 147: 794 (1987).PubMedCrossRefGoogle Scholar
  17. 17.
    N.D. Lees, M.C. Broughton, D. Sanglard and M. Bard, Azole susceptibility and hyphal formation in a cytochrome P-450-deficient mutant of C. albicans, Antimicrob. Ag. Chemother. 34: 831 (1990).CrossRefGoogle Scholar
  18. 18.
    A.B. Orth and H.D. Sisler, Mode of action of terbinafine in Ustilago maydis and characterization of resistant mutants, Pestic. Biochem. Physiol. 37: 53 (1990).CrossRefGoogle Scholar
  19. 19.
    H.D. Sisler, R.C. Walsh and B.N. Ziogas, Ergosterol biosynthesis: a target of fungitoxic action, in: “IUPAC Pesticide Chemistry: Human Welfare and the Environment”, Vol. 3, “Mode of Action, Metabolism and Toxicology”, S. Matsunaka, D.H. Hutson and S.D. Murphy, eds., Pcrgamon Press, Oxford (1983).Google Scholar
  20. 20.
    Y. Yoshida and A. Aoyama, Cytochromes P-450 in the ergosterol biosynthesis, in: “Frontiers in Bio transformation”, Vol. 4, “Microbial and Plant Cytochromes P-450: Biochemical Characteristics, Genetics Engineering and Practical Implications”, K. Ruckpaul and H. Rein, eds., Akademic Verlag, Berlin (1991).Google Scholar
  21. 21.
    H. Vanden Bossche, P. Marichal, M-C. Coene, G. Willemsens, L.Le Jeune, W. Cools and H.Verhoeven, Cytochrome P450-dependent 14oc-demethylase-Target for antifungal agents and herbicides, in: “Regulation of Isopentenoid Metabolism”, W.D. Nes, E.J. Parish and J.M. Trzaskos, eds., American Chemical Society, Washington DC (1992).Google Scholar
  22. 22.
    P.F. Watson, M.E. Rose, S.W. Ellis, H. England and S.L. Kelly, Defective sterol C5–6 desaturation and azole resistance: a new hypothesis for the mode of action of azole antifungals, Biochem. Biophys. Res. Commun. 15: 1170 (1989).CrossRefGoogle Scholar
  23. 23.
    S.L. Kelly, J. Rowe and P.F. Watson, Molecular genetic studies on the mode of action of azole antifungal agents, Biochem. Soc. Trans 19: 796 (1991).PubMedGoogle Scholar
  24. 24.
    W.R. Nes, B.C. Sekula, W.D. Nes and J.H. Adler, The functional importance of structural features of ergosterol in yeast, J. Biol. Chem. 253: 6218 (1978).PubMedGoogle Scholar
  25. 25.
    A.K. Lala, H.K. Lin and K. Bloch, The effect of some alkyl derivatives of cholesterol on the permeability properties and microviscosities of model membranes, Bioorganic Chem. 7: 437 (1978).CrossRefGoogle Scholar
  26. 26.
    B.N. Ziogas, H.D. Sisler and W.R. Lusby, Sterol content and other characteristics of pimaricin-resistant mutants of Aspergillus nidulans, Pestic. Biochem. Physiol. 20: 320 (1983).CrossRefGoogle Scholar
  27. 27.
    D. Barug and A. Kerkenaar, Resistance in mutagen-induced mutants of Ustilago maydis to fungicides which inhibit ergosterol biosynthesis, Pestic Sci. 15: 78 (1984).CrossRefGoogle Scholar
  28. 28.
    J. Guan, A. Kerkenaar and M.A. De Waard, Studies on mechanism of resistance to imazalil in Penicillium italicum, Tag.-Ber. Acad. Landwirtsch. Wiss. Berlin 291: 115 (1990).Google Scholar
  29. 29.
    J. Van Cutsem, The in vitro antifungal spectrum of itraconazole, Mycoses 32 (Suppl. 1): 7 (1989).PubMedGoogle Scholar
  30. 30.
    N.S. Ryder, Terbinafine: mode of action and properties of the squalene epoxidase inhibition, Brit. J. Dermatol. 126 (Suppl. 39): 2 (1992).CrossRefGoogle Scholar
  31. 31.
    A. Polak, Amorolfine, RO 14–4767/002, Loceryl, in: “Recent Progress in Antifungal Chemotherapy”, H. Yamaguchi, G.S. Kobayashi and H. Takahashi, eds., Marcel Dekker Inc., New York (1991).Google Scholar
  32. 32.
    D.G. Gottlieb, R.J. Knaus and S.G. Wood, Differences in the sterol synthesizing pathways of sterol-producing and non-sterol-producing fungi, Phytophatology 68: 1168 (1978).CrossRefGoogle Scholar
  33. 33.
    C.G. Elliott, M.E. Hendrie, B.A. Knights and W. Parker, A steroid growth factor requirement in a fungus, Nature 203: 427 (1964).CrossRefGoogle Scholar
  34. 34.
    W.D. Nes, G.A. Saunders and E. Heftman, Role of steroids and triterpenoids in the growth and reproduction of Phytophthora cacturum, Lipids 17: 178 (1982).CrossRefGoogle Scholar
  35. 35.
    H. Vanden Bossche and P. Marichal, Mode of action of anti-Candida drugs: focus on terconazole and other ergosterol biosynthesis inhibitors, Am. J. Obstet. Gynecol. 165: 1193 (1991).CrossRefGoogle Scholar
  36. 36.
    H. Vanden Bossche, W. Lauwers, G. Willemsens, P. Marichal, F. Cornelissen and W. Cools, Molecular basis for the antimycotic and antibacterial activity of N-substituted imidazoles and triazoles: the inhibition of isoprenoid biosynthesis, Pestic Sci. 15: 188 (1984).CrossRefGoogle Scholar
  37. 37.
    C. Marcireau, M. Guilloton and F. Karst, In vivo effects of fenpropimorph on the yeast Saccharomyces cerevisiae and determination of the molecular basis of the antifungal property, Antimicrob. Ag. Chemother. 34: 989 (1990).CrossRefGoogle Scholar
  38. 38.
    J.D. Weete and M.L. Wise, Effects of triazoles on fungi. V. Response by a naturally tolerant species, Mucor rouxii, Exptl. Mycol. 11: 214 (1987).CrossRefGoogle Scholar
  39. 39.
    M. Sancholle, J.D. Weete and C. Montant, Effect of triazoles on fungi. I. Growth and cellular permeability, Pestic Biochem. Physiol. 21: 31 (1984).CrossRefGoogle Scholar
  40. 40.
    H. Vanden Bossche, Ergosterol biosynthesis inhibitors, in: “Candida albicans ,Cellular and Molecular Biology”, R. Prassad, ed., Springer Verlag, Berlin (1991).Google Scholar
  41. 41.
    M. Orlowski, Mucor dimorphism, Microb. Rev. 55: 234 (1991).Google Scholar
  42. 42.
    L.W. Parks, R.J. Rodriguez and C. Low, An essential fungal growth factor derived from ergosterol: a new end product of sterol biosynthesis in fungi? Lipids 21: 89 (1986).PubMedCrossRefGoogle Scholar
  43. 43.
    S. Kawasaki, M. Ramgopal, J. Chin and K. Bloch, Sterol control of the phosphatidylethanolamine-phosphatidylcholine conversion in the yeast mutant GL7, Proc. Natl. Acad. Sci. USA 82: 5715 (1985).PubMedCrossRefGoogle Scholar
  44. 44.
    C. Dahl, H.-P. Biemann and J. Dahl, A protein kinase antigenically related to pp60v-src possibly involved in yeast cell cycle control: positive in vivo regulation by sterol, Proc. Natl. Acad. Sci. USA 84: 4012 (1987).PubMedCrossRefGoogle Scholar
  45. 45.
    K. Bloch, Lipid structure and function, in: “Lipids and Membranes: Past, Present and Future”, J.A.F. Op den Kamp, B. Roelofsen and K.W.A. Wirtz, eds., Elsevier Science Publishers B.V., Amsterdam (1986).Google Scholar
  46. 46.
    W.D. Nes, P.K. Hanners and E.J. Parish, Control of fungal sterol C-24 transalkylation: importance to developmental regulation, Biochem. Biophys. Res. Commun. 139: 410 (1986).PubMedCrossRefGoogle Scholar
  47. 47.
    R.J. Rodriguez, C. Low, C.D.K. Bottema and L.W. Parks, Multiple functions for sterols in Saccharomyces cerevisiae, Biochim. Biophys. Ada 837: 336 (1985).CrossRefGoogle Scholar
  48. 48.
    N.D. Lees, B.A. Arlington and M. Bard, Genetics and molecular biology of the genes functioning late in the sterol biosynthetic pathway of Saccharomyces ,in: “Regulation of Isopentenoid Metabolism”, W.D. Nes, E.J. Parish and J.M. Trzaskos, eds., American Chemical Society, Washington DC (1992).Google Scholar
  49. 49.
    W.J. Pinto and W.R. Nes, Stereochemical specificity for sterols in Saccharomyces cerevisiae, J. Biol. Chem. 258: 4472 (1983).PubMedGoogle Scholar
  50. 50.
    R. Ghraf, E.R. Lax, S. Oza and H. Schriefers, Transformation of C18-, C9-and C21-steroids by cultures of Candida albicans, J. Steroid Biochem. 6: 1531 (1975).PubMedCrossRefGoogle Scholar
  51. 51.
    P. Marichal, J. Gorrens, J. Van Cutsem and H. Vanden Bossche, Culture media for the study of the effects of azole derivatives on germ tube formation and hyphal growth of C. albicans ,Mycoses 29: 76 (1985).CrossRefGoogle Scholar
  52. 52.
    D.S. Loose, D.J. Schurman and D. Feldman, A corticosteroid binding protein and endogenous ligand in C. albicans indicating a possible steroid-receptor system, Nature 293: 477 (1981).PubMedCrossRefGoogle Scholar
  53. 53.
    D.S. Loose and D. Feldman, Characterization of a unique corticosterone-binding protein in Candida albicans, J. Biol. Chem. 257: 4925 (1982).PubMedGoogle Scholar
  54. 54.
    E.P. Stover, D.S. Loose, D.A. Stevens and D. Feldman, Ketoconazole binds to the intracellular corticosteroid-binding protein in Candida albicans, Biochem. Biophys. Res. Commun. 117: 43 (1983).PubMedCrossRefGoogle Scholar
  55. 55.
    M. Schaude, H. Ackerbauer and H. Mieth, Inhibitory effect of antifungal agents on germ tube formation in Candida albicans, Mycoses 30: 281 (1987).CrossRefGoogle Scholar
  56. 56.
    P.L. Powell, C.L. Frey and D.J. Drutz, Identification of a 17ß-estradiol binding protein in Candida albicans and Candida (Torulopsis) glabrata, Exptl. Mycol. 8: 304 (1984).CrossRefGoogle Scholar
  57. 57.
    R. Skowronski and D. Feldman, Characterization of an estrogen-binding protein in the yeast Candida albicans, Endocrinology 124: 1965 (1989).PubMedCrossRefGoogle Scholar
  58. 58.
    B.L. Powell, D.J. Drutz, M. Huppert and S.H. Sun, Relationship of progesterone-and estradiol-binding proteins in Coccidioides immitis to coccidioidal dissemination in pregnancy, Infect. Immun. 40: 478 (1983).PubMedGoogle Scholar
  59. 59.
    B.L. Powell and D.J. Drutz, Identification of a high-affinity binder for estradiol and a low-affinity binder for testosterone in Coccidioides immitis, Infect. Immun. 45: 784 (1984).PubMedGoogle Scholar
  60. 60.
    A. Burshell, P.A. Stathis, Y. Do, S.C. Miller and D. Feldman, Characterization of an estrogen-binding protein in the yeast Saccharomyces cerevisiae, J. Biol. Chem. 259: 3450 (1984).PubMedGoogle Scholar
  61. 61.
    D.S. Loose, E.P. Stover, A. Restrepo, D.A. Stevens and D. Feldman, Estradiol binds to a receptor-like cytosol binding protein and initiates a biological response in Paracoccidioides brasiliensis, Proc. Natl. Acad. Sci. USA 80: 7659 (1983).PubMedCrossRefGoogle Scholar
  62. 62.
    A. Restrepo, M.E. Salazar, L.E. Cano, E.P. Stover, D. Feldman and D.A. Stevens, Estrogens inhibit mycelium-to-yeast transformation in the fungus Paracoccidioides brasiliensis: implications for resistance of females to Paracoccidioidomycosis, Infect. Immun. 46: 346 (1984).PubMedGoogle Scholar
  63. 63.
    OS. Kinsman, K. Pitblado and C.J. Coulson, Effect of mammalian steroid hormones and luteinizing hormone on the germination of Candida albicans and implications for vaginal candidosis, Mycoses 31: 617 (1988).PubMedCrossRefGoogle Scholar
  64. 64.
    J.H. Reinhardt, A.M. Allen, D. Gunnison and W.A. Akers, Experimental human Trichophyton mentagrophytes infections, J. Invest. Derm. 62: 419 (1974).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Hugo Vanden Bossche
    • 1
  • Patrick Marichal
    • 1
  1. 1.Department of Comparative BiochemistryJanssen Research FoundationBeerseBelgium

Personalised recommendations