In vivo effects of fenpropimorph on the yeast Saccharomyces cerevisiae and determination of the molecular basis of the antifungal property

The effects of fenpropimorph on sterol biosynthesis and growth of Saccharomyces cerevisiae were examined to pinpoint the mode of action of fungicides that inhibit ergosterol biosynthesis. Taking advantage of sterol auxotrophy and sterol permeability in mutant strains, we show that growth inhibition is strongly correlated with inhibition of sterol biosynthesis. We confirm that in vivo and at low concentrations, fenpropimorph inhibits delta 8----delta 7-sterol isomerase, and in addition, when it is used at higher concentrations, it inhibits delta 14-sterol reductase. We show also that the fungistatic effect of fenpropimorph is not due to the accumulation of abnormal sterols in treated cells but is linked to the specific inhibition of ergosterol biosynthesis, leading to the arrest of cell proliferation in the unbudded G1 phase of the cell cycle.

[1]  B. C. Baldwin,et al.  The intracellular location and physiological effects of abnormal sterols in fungi grown in the presence of morpholine and functionally related fungicides , 1989 .

[2]  H. Biemann,et al.  A protein kinase antigenically related to pp60v-src possibly involved in yeast cell cycle control: positive in vivo regulation by sterol. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[3]  E. Mercer,et al.  Inhibition of sterol Δ8 → Δ7-isomerase and Δ14-reductase by fenpropimorph tridemorph and fenpropidin in cell-free enzyme systems from Saccharomyces cerevisiae , 1987 .

[4]  F. Karst,et al.  Regulation of early enzymes of ergosterol biosynthesis in Saccharomyces cerevisiae. , 1986, The Biochemical journal.

[5]  L. W. Parks,et al.  Multiple functions for sterols in Saccharomyces cerevisiae. , 1985, Biochimica et biophysica acta.

[6]  J. Camonis,et al.  Contrôle du cycle de division cellulaire et de la sporulation chez Saccharomyces cerevisiae par le système de l'AMP cyclique , 1985 .

[7]  L. W. Parks,et al.  Yeast sterols: yeast mutants as tools for the study of sterol metabolism. , 1985, Methods in enzymology.

[8]  A. Kerkenaar,et al.  Effect of fenpropimorph and imazalil on sterol biosynthesis in penicillium italicum , 1984 .

[9]  Brian C. Baldwin,et al.  Inhibition of ergosterol biosynthesis in Saccharomyces cerevisiae and Ustilago maydis by tridemorph, fenpropimorph and fenpropidin , 1984 .

[10]  L. W. Parks,et al.  Relationship between antifungal activity and inhibition of sterol biosynthesis in miconazole, clotrimazole, and 15-azasterol , 1983, Antimicrobial Agents and Chemotherapy.

[11]  K. Bloch,et al.  Sterol synergism in yeast. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[12]  P. Leroux,et al.  Etudes sur les inhibiteurs de la biosynthèse des stérols fongiques : I. - Fongicides provoquant l'accumulation de desméthylstérols , 1983 .

[13]  G. Schroepfer,et al.  Sterol biosynthesis. , 1981, Annual review of biochemistry.

[14]  H. van den Bossche,et al.  In vitro and in vivo effects of the antimycotic drug ketoconazole on sterol synthesis , 1980, Antimicrobial Agents and Chemotherapy.

[15]  C. Woloshuk,et al.  Mode of Action of the Azasteroid Antibiotic 15-Aza-24-Methylene-d-Homocholesta-8,14-Dien-3β-ol in Ustilago maydis , 1979, Antimicrobial Agents and Chemotherapy.

[16]  F. Karst,et al.  Ertosterol biosynthesis in Saccharomyces cerevisiae: mutants deficient in the early steps of the pathway. , 1977, Molecular & general genetics : MGG.

[17]  M. Bard,et al.  BIOSYNTHESIS OF TERPENES AND STEROIDS PART 9, THE STEROLS OF SOME MUTANT YEASTS AND THEIR RELATIONSHIP TO THE BIOSYNTHESIS OF ERGOSTEROL , 1974 .

[18]  R. A. Woods.  Nystatin-Resistant Mutants of Yeast: Alterations in Sterol Content , 1971, Journal of bacteriology.

[19]  L. Dorfman.  Ultraviolet Absorption of Steroids. , 1953 .