Mechanism of Fungal Growth Suppression by Inhibitors of Ergosterol Biosynthesis

Weete, John D.

doi:10.1021/bk-1987-0325.ch017

Cited by 33 publications

(10 citation statements)

References 51 publications

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“…The modification of the lipidic environment in membranes may therefore be harmful to cell viability (24,25). Several antimicrobial molecules have been found to interfere with lipid metabolism or directly with specific lipid molecules (26,27). Recently, new fatty acids with antifungal activity were isolated and characterized from liquid cultures of the biocontrol agent S. flocculosa (6,7).…”

Section: Discussionmentioning

confidence: 99%

Influence of a subinhibitory dose of antifungal atty acids fromSporothrix flocculosa on cellular lipid composition in fungi

Benyagoub

Willemot

Bélanger

1996

Lipids

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Antifungal fatty acids produced by the biocontrol fungus Sporothrix flocculosa were studied on the basis of their effect on growth and cellular lipid composition of three fungi, Cladosporium cucumerinum, Fusarium oxysporum, and S. flocculosa, whose growth was decreased by 51, 33, and 5%, respectively, when exposed to 0.4 mg fatty acid per ml. The sensitivity to fatty acid antibiotics from S. flocculosa was related to a high degree of unsaturation of phospholipid fatty acids and a low proportion of sterols. The major responses of sensitive fungi to sublethal doses of antifungal fatty acids from liquid culture of S. flocculosa were: (i) a decrease in total lipid; (ii) an increase in the degree of fatty acid unsaturation (18:1 > 18:2 > 18:3); (iii) an increase in free fatty acids and phosphatidic acid and a decrease in total phospholipids; and (iv) an increase in sterol/phospholipid ratio. These modifications in lipid composition led to an increase in membrane fluidity in sensitive fungi as demonstrated by assessment of fluoresence anisotropy using liposomes and 1,6-diphenyl-1,3,5-hexatriene probe. This alteration in the physical state of lipids appears to be responsible for the previously demonstrated alteration of membrane structure and function in fungi confronted to S. flocculosa.

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Section: Discussionmentioning

confidence: 99%

Influence of a subinhibitory dose of antifungal atty acids fromSporothrix flocculosa on cellular lipid composition in fungi

Benyagoub

Willemot

Bélanger

1996

Lipids

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“…As the phospholipid fractions fi'otn tniconazole-treated cells were shown to contain similar relative proportions of saturated Cr^ and C|g fatty acids to those exhibited by phospholipid fractions firom control cultures, such changes in the oleic acid content may be accounted for by decreased A12 desaturase activity as a result of altered cellular free sterol composition. Alterations in fatty acid desaturase activities in response to changes in cellular sterol content and/or composition have been well documented for a variety of cell types (Freter et al 1979, Utneki and Nozawa 1983, Weete 1987).…”

Section: Discussionmentioning

confidence: 99%

Phosphatidylcholine biosynthesis and cell growth in Apium graveolens

Parkin¹,

Goad²,

Rolph³

1995

Physiol Plant

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1995. Phosphatidylcholine biosynthesis and cell growth in Apium graveolens. -Ptiysioi. Plant. 94; 643-650.Xenobiotics directed against sterol biosynthesis have proved to be useful tools in the determination of which sterol molecules are necessary for successful plant cell growth. However, the exact mode of action by which sterols are able to trigger cell growth remains to be elucidated. Previous studies using the triazole paclobutrazol, demonstrated that in Apium graveolens (cv. New Dwarf White) suspension cultures, sterol and phosphatidylcholine biosynthesis are co-ordinately regulated (C. E. Rolph and L. i. Goad 1991, Physiol. Plant. 83; 605-610). The studies presented herein, were designed to investigate the possible role of phosphatidylcholine in the stimulation of plant cell growth. Sterol biosynthesis, and hence eel] growth, was inhibited by the use of the azole xenobiotic miconazole. Treatment of tbe cultures with miconazole lead to compositional changes in die free sterol content of the cells. For example, 30 jiM miconazole treatment led to a reduction in the stigmasterol/sitosterol ratios from 1.53 to 1.24. In contrast, the phospholipid content of the cells remained relatively unchanged with phosphatidyicholine accounting for approximately 25% of the total phospholipids present in both control and miconazole-treated cells. The cytostatic effect of miconazole could be partially counteracted by supplementation of the growth medium with the phytosterol stigmasterol and/or the unsaturated fatty acids oleate and linoleate. The activity of CTP;cholinephosphate cytidylyltransferase (EC 2.7.7.15), a rate-limiting enzyme in phosphatidylcholine biosynthesis, was significantly reduced in cells whose growth had been arrested by micotiazole treatment. In tniconazole-treated cultures whose growth had been partially restored by supplementation with either specific sterols or unesterified fatty acids, the activity of diis key enzyme was increa.sed. In the case of stigmasterol, oleate and linoleate supplementation, the microsomal activity was found to be similar to that exhibited by control cultures. From these studies, it may be concluded that certain phytosterols and unsaturated fatty acids play key roles with respect to phosphatidylcholine biosynthesis and that phosphatidylcholine biosynthesis via the CDP-base pathway is an important pre-and/or co-requisite for successful culture growth.

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“…Moreover, 14a-methyl-fecosterol, 24-25 dihydrolanosterol and lanosterol increased. This methyl sterol accumulation in the cells would lead to reduction of the plasma membrane fluidity (Block 1979;Weete 1987;Vanden Bossche 1985).…”

Section: Discussionmentioning

confidence: 99%

“…1980). Moreover, the ergosterol and the unsaturated fatty acid levels are related, and both modulate the membrane fluidity (Bottema et al 1985;Vanden Bossche 1985;Weete 1987). Our study describes the effect of flusilazole, a triazole fungicide, on ergosterol and fatty acid metabolism of S. cereoisiae.…”

mentioning

confidence: 87%