Evaluation of fungicides for curative activity against Tranzschelia discolor, cause of the rust disease of French prune (Prunus domestica L.)

1987 ◽  
Vol 38 (3) ◽  
pp. 577 ◽  
Author(s):  
PF Kable ◽  
BJ Keen ◽  
RW Bambach
Keyword(s):  
Latent Period ◽  
Ergosterol Biosynthesis ◽  
Prunus Domestica ◽  
Rust Disease ◽  
Foliar Sprays ◽  
Ergosterol Biosynthesis Inhibitors ◽  
Biosynthesis Inhibitors ◽  
Lesion Growth ◽  
Tranzschelia Discolor

The ergosterol biosynthesis inhibitors, propiconazole, RH-2161 and RH-3866, exhibited strong curative activity against Tranzschelia discolor infections in French prune leaves. Foliar sprays (25-50 ppm) applied during the latent period, up to 7 days after inoculation, completely suppressed the disease. When these fungicides were applied after the appearance of symptoms, they inhibited further lesion growth and sporulation. Other fungicides having some curative activity were triforine and oxycarboxin. Fungicides with little or no curative activity against T. discolor were bitertanol, PP969, triadimefon and tridemorph.

scholarly journals Ergosterol Biosynthesis Inhibitors Become Fungicidal when Combined with Calcineurin Inhibitors against Candida albicans, Candida glabrata, and Candida krusei

2003 ◽  
Vol 47 (3) ◽  
pp. 956-964 ◽  
Author(s):  
Chiatogu Onyewu ◽  
Jill R. Blankenship ◽  
Maurizio Del Poeta ◽  
Joseph Heitman
Keyword(s):  
Candida Albicans ◽  
Antifungal Agents ◽  
Calcineurin Inhibitors ◽  
Therapeutic Window ◽  
Ergosterol Biosynthesis ◽  
Drug Synergism ◽  
Wild Type ◽  
Ergosterol Biosynthesis Inhibitors ◽  
Biosynthesis Inhibitors ◽  
Mutant Strains

ABSTRACT Azoles target the ergosterol biosynthetic enzyme lanosterol 14α-demethylase and are a widely applied class of antifungal agents because of their broad therapeutic window, wide spectrum of activity, and low toxicity. Unfortunately, azoles are generally fungistatic and resistance to fluconazole is emerging in several fungal pathogens. We recently established that the protein phosphatase calcineurin allows survival of Candida albicans during the membrane stress exerted by azoles. The calcineurin inhibitors cyclosporine A (CsA) and tacrolimus (FK506) are dramatically synergistic with azoles, resulting in potent fungicidal activity, and mutant strains lacking calcineurin are markedly hypersensitive to azoles. Here we establish that drugs targeting other enzymes in the ergosterol biosynthetic pathway (terbinafine and fenpropimorph) also exhibit dramatic synergistic antifungal activity against wild-type C. albicans when used in conjunction with CsA and FK506. Similarly, C. albicans mutant strains lacking calcineurin B are markedly hypersensitive to terbinafine and fenpropimorph. The FK506 binding protein FKBP12 is required for FK506 synergism with ergosterol biosynthesis inhibitors, and a calcineurin mutation that confers FK506 resistance abolishes drug synergism. Additionally, we provide evidence of drug synergy between the nonimmunosuppressive FK506 analog L-685,818 and fenpropimorph or terbinafine against wild-type C. albicans. These drug combinations also exert synergistic effects against two other Candida species, C. glabrata and C. krusei, which are known for intrinsic or rapidly acquired resistance to azoles. These studies demonstrate that the activity of non-azole antifungal agents that target ergosterol biosynthesis can be enhanced by inhibition of the calcineurin signaling pathway, extending their spectrum of action and providing an alternative approach by which to overcome antifungal drug resistance.

Synthesis of 6(α,β)-aminocholestanols as ergosterol biosynthesis inhibitors

1998 ◽  
Vol 8 (24) ◽  
pp. 3627-3630 ◽  
Author(s):  
Pierre Beuchet ◽  
Laïla El kihel ◽  
Michel Dherbomez ◽  
Georges Charles ◽  
Yves Letourneux
Keyword(s):  
Ergosterol Biosynthesis ◽  
Ergosterol Biosynthesis Inhibitors ◽  
Biosynthesis Inhibitors

scholarly journals Characterization of Squalene Epoxidase of Saccharomyces cerevisiae by Applying Terbinafine-Sensitive Variants

2006 ◽  
Vol 51 (1) ◽  
pp. 275-284 ◽  
Author(s):  
Christoph Ruckenstuhl ◽  
Silvia Lang ◽  
Andrea Poschenel ◽  
Armin Eidenberger ◽  
Pravas Kumar Baral ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Amino Acids ◽  
Nucleotide Binding ◽  
Ergosterol Biosynthesis ◽  
Squalene Epoxidase ◽  
In Vitro Mutagenesis ◽  
Mrna Levels ◽  
Ergosterol Biosynthesis Inhibitors ◽  
Biosynthesis Inhibitors

ABSTRACT Squalene epoxidase (SE) is the target of terbinafine, which specifically inhibits the fungal enzyme in a noncompetitive manner. On the basis of functional homologies to p-hydroxybenzoate hydroxylase (PHBH) from Pseudomonas fluorescens, the Erg1 protein contains two flavin adenine dinucleotide (FAD) domains and one nucleotide binding (NB) site. By in vitro mutagenesis of the ERG1 gene, which codes for the Saccharomyces cerevisiae SE, we isolated erg1 alleles that conferred increased terbinafine sensitivity or that showed a lethal phenotype when they were expressed in erg1-knockout strain KLN1. All but one of the amino acid substitutions affected conserved FAD/nucleotide binding sites. The G25S, D335X (W, F, P), and G210A substitutions in the FADI, FADII, and NB sites, respectively, rendered the SE variants nonfunctional. The G30S and L37P variants exhibited decreased enzymatic activity, accompanied by a sevenfold increase in erg1 mRNA levels and an altered sterol composition, and rendered KLN1 more sensitive not only to allylamines (10 to 25 times) but also to other ergosterol biosynthesis inhibitors. The R269G variant exhibited moderately reduced SE activity and a 5- to 10-fold increase in allylamine sensitivity but no cross-sensitivity to the other ergosterol biosynthesis inhibitors. To further elucidate the roles of specific amino acids in SE function and inhibitor interaction, a homology model of Erg1p was built on the basis of the crystal structure of PHBH. All experimental data obtained with the sensitive Erg1 variants support this model. In addition, the amino acids responsible for terbinafine resistance, although they are distributed along the sequence of Erg1p, cluster on the surface of the Erg1p model, giving rise to a putative binding site for allylamines.

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