Dual Effects of Plant Steroidal Alkaloids on Saccharomycescerevisiae

Abstract

Many plant species accumulate sterols and triterpenes as antimicrobial glycosides. These secondary metabolites (saponins) provide built-in chemical protection against pest and pathogen attack and can also influence induced defense responses. In addition, they have a variety of important pharmacological properties, including anticancer activity. The biological mechanisms underpinning the varied and diverse effects of saponins on microbes, plants, and animals are only poorly understood despite the ecological and pharmaceutical importance of this major class of plant secondary metabolites. Here we have exploited budding yeast (Saccharomyces cerevisiae) to investigate the effects of saponins on eukaryotic cells. The tomato steroidal glycoalkaloid ␣-tomatine has antifungal activity towards yeast, and this activity is associated with membrane permeabilization. Removal of a single sugar from the tetrasaccharide chain of ␣-tomatine results in a substantial reduction in antimicrobial activity. Surprisingly, the complete loss of sugars leads to enhanced antifungal activity. Experiments with ␣-tomatine and its aglycone tomatidine indicate that the mode of action of tomatidine towards yeast is distinct from that of ␣-tomatine and does not involve membrane permeabilization. Investigation of the effects of tomatidine on yeast by gene expression and sterol analysis indicate that tomatidine inhibits ergosterol biosynthesis. Tomatidine-treated cells accumulate zymosterol rather than ergosterol, which is consistent with inhibition of the sterol C 24 methyltransferase Erg6p. However, erg6 and erg3 mutants (but not erg2 mutants) have enhanced resistance to tomatidine, suggesting a complex interaction of erg mutations, sterol content, and tomatidine resistance.Plants produce a vast array of structurally diverse secondary metabolites. These natural products serve as attractants for agents that mediate pollination and seed dispersal; they also provide chemical defenses against pests, pathogens, and invasion by neighboring plants (47). Small molecules therefore play key roles in ecological interactions between plants and other organisms. We exploit the rich reservoir of metabolic diversity provided to us by diverse plant species in order to find new drugs and other valuable compounds. The chemical "space," in terms of the number and variety of molecules produced by plants, is enormous. Structures of over 100,000 diverse compounds have been reported so far (11), and this is inevitably just the tip of the iceberg. However, with a few well-characterized exceptions, we know very little about the biological properties of plant secondary metabolites. Characterization of the biological activities of these compounds will be critical, both from an ecological perspective and a pharmaceutical perspective.The terpenes are one of the largest and most diverse groups of plant secondary metabolites (9). They include sterols and triterpenes, complex compounds that are formed by the cyclization of 2,3-oxidosqualene. Sterols and triterpenes can accumulat...

Development of Practical HPLC Methods for the Separation and Determination of Eggplant Steroidal Glycoalkaloids and their Aglycones

“…Progesterone, an animal hormone, was considered a good choice for an internal standard because it is not expected to be present in the eggplant sample and was not found in the extracts obtained. Cholesterol [60] and nicotine [61] have been applied as internal standards for the determination of Solanum glycoalkaloids. However, although they are normally considered to be present only in small quantities, researchers outside this field of study have noted that plants can contain cholesterol.…”

Use of ‘natural’ products as alternatives to antibiotic feed additives in ruminant production

“…The foaming property of saponins increases the surface tension of the bulk solution and accelerates lysis of microbial cells with weakened membranes. In addition, bacterial growth inhibition may be caused by complexation of essential minerals and steroids with saponins, thus limiting their bioavailability for bacterial metabolism (West et al, 1978;Simons et al, 2006).…”

The CAP protein superfamily: function in sterol export and fungal virulence

“…Sterol metabolism is a known Achilles heel of fungi and acts as a major fungicide target in medicine and agriculture (36). Intriguingly, plants have exploited ergosterol binding in the fungal membrane as a mechanism of antifungal phytoalexins such as the tomato glycoalkaloid tomatine (37). The finding that secreted CAP proteins are conserved fungal virulence factors suggests that they could serve as potential targets to reduce fungal infection.…”