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Appl Environ Microbiol. 1996 Nov; 62(11): 3960–3966.
PMCID: PMC168214

Copper toxicity towards Saccharomyces cerevisiae: dependence on plasma membrane fatty acid composition.


One major mechanism of copper toxicity towards microorganisms is disruption of plasma membrane integrity. In this study, the influence of plasma membrane fatty acid composition on the susceptibility of Saccharomyces cerevisiae to Cu2+ toxicity was investigated. Microbial fatty acid composition is highly variable, depending on both intrinsic and environmental factors. Manipulation was achieved in this study by growth in fatty acid-supplemented medium. Whereas cells grown under standard conditions contained only saturated and monounsaturated fatty acids, considerable incorporation of the diunsaturated fatty acid linoleate (18:2) (to more than 65% of the total fatty acids) was observed in both whole-cell homogenates and plasma membrane-enriched fractions from cells grown in linoleate-supplemented medium. Linoleate enrichment had no discernible effect on the growth of S. cerevisiae. However, linoleate-enriched cells were markedly more susceptible to copper-induced plasma membrane permeabilization. Thus, after addition of Cu(NO3)2, rates of cellular K+ release (loss of membrane integrity) were at least twofold higher from linoleate-supplemented cells than from unsupplemented cells; this difference increased with reductions in the Cu2+ concentration supplied. Levels of cellular Cu accumulation were also higher in linoleate-supplemented cells. These results were correlated with a very marked dependence of whole-cell Cu2+ toxicity on cellular fatty acid unsaturation. For example, within 10 min of exposure to 5 microM Cu2+, only 3% of linoleate-enriched cells remained viable (capable of colony formation). In contrast, 100% viability was maintained in cells previously grown in the absence of a fatty acid supplement. Cells displaying intermediate levels of linoleate incorporation showed intermediate Cu2+ sensitivity, while cells enriched with the triunsaturated fatty acid linolenate (18:3) were most sensitive to Cu2+. These results demonstrate for the first time that changes in cellular and plasma membrane fatty acid compositions can dramatically alter microbial sensitivity to copper.

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Selected References

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  • Aßmann S, Sigler K, Höfer M. Cd2+-induced damage to yeast plasma membrane and its alleviation by Zn2+: studies on Schizosaccharomyces pombe cells and reconstituted plasma membrane vesicles. Arch Microbiol. 1996 Apr;165(4):279–284. [PubMed]
  • Avery SV, Lloyd D, Harwood JL. Temperature-dependent changes in plasma-membrane lipid order and the phagocytotic activity of the amoeba Acanthamoeba castellanii are closely correlated. Biochem J. 1995 Dec 15;312(Pt 3):811–816. [PMC free article] [PubMed]
  • Avery SV, Tobin JM. Mechanism of adsorption of hard and soft metal ions to Saccharomyces cerevisiae and influence of hard and soft anions. Appl Environ Microbiol. 1993 Sep;59(9):2851–2856. [PMC free article] [PubMed]
  • Awaya J, Ohno T, Ohno H, Omura S. Substitution of cellular fatty acids in yeast cells by the antibiotic cerulenin and exogenous fatty acids. Biochim Biophys Acta. 1975 Dec 17;409(3):267–273. [PubMed]
  • BLIGH EG, DYER WJ. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. [PubMed]
  • Bossie MA, Martin CE. Nutritional regulation of yeast delta-9 fatty acid desaturase activity. J Bacteriol. 1989 Dec;171(12):6409–6413. [PMC free article] [PubMed]
  • Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. [PubMed]
  • Cervantes C, Gutierrez-Corona F. Copper resistance mechanisms in bacteria and fungi. FEMS Microbiol Rev. 1994 Jun;14(2):121–137. [PubMed]
  • Culotta VC, Joh HD, Lin SJ, Slekar KH, Strain J. A physiological role for Saccharomyces cerevisiae copper/zinc superoxide dismutase in copper buffering. J Biol Chem. 1995 Dec 15;270(50):29991–29997. [PubMed]
  • Greco MA, Hrab DI, Magner W, Kosman DJ. Cu,Zn superoxide dismutase and copper deprivation and toxicity in Saccharomyces cerevisiae. J Bacteriol. 1990 Jan;172(1):317–325. [PMC free article] [PubMed]
  • Hazel JR, Williams EE. The role of alterations in membrane lipid composition in enabling physiological adaptation of organisms to their physical environment. Prog Lipid Res. 1990;29(3):167–227. [PubMed]
  • Lin CM, Crawford BF, Kosman DJ. Distribution of 64Cu in Saccharomyces cerevisiae: kinetic analyses of partitioning. J Gen Microbiol. 1993 Jul;139(7):1617–1626. [PubMed]
  • McDonough VM, Stukey JE, Martin CE. Specificity of unsaturated fatty acid-regulated expression of the Saccharomyces cerevisiae OLE1 gene. J Biol Chem. 1992 Mar 25;267(9):5931–5936. [PubMed]
  • Mills DE, Murthy M, Galey WR. Dietary fatty acids, membrane transport, and oxidative sensitivity in human erythrocytes. Lipids. 1995 Jul;30(7):657–663. [PubMed]
  • Murata N. Low-temperature effects on cyanobacterial membranes. J Bioenerg Biomembr. 1989 Feb;21(1):61–75. [PubMed]
  • Ohsumi Y, Kitamoto K, Anraku Y. Changes induced in the permeability barrier of the yeast plasma membrane by cupric ion. J Bacteriol. 1988 Jun;170(6):2676–2682. [PMC free article] [PubMed]
  • PASSOW H, ROTHSTEIN A. The binding of mercury by the yeast cell in relation to changes in permeability. J Gen Physiol. 1960 Jan;43:621–633. [PMC free article] [PubMed]
  • Rego AC, Oliveira CR. Dual effect of lipid peroxidation on the membrane order of retinal cells in culture. Arch Biochem Biophys. 1995 Aug 1;321(1):127–136. [PubMed]
  • Serrano R. H+-ATPase from plasma membranes of Saccharomyces cerevisiae and Avena sativa roots: purification and reconstitution. Methods Enzymol. 1988;157:533–544. [PubMed]
  • Stohs SJ, Bagchi D. Oxidative mechanisms in the toxicity of metal ions. Free Radic Biol Med. 1995 Feb;18(2):321–336. [PubMed]
  • Stukey JE, McDonough VM, Martin CE. Isolation and characterization of OLE1, a gene affecting fatty acid desaturation from Saccharomyces cerevisiae. J Biol Chem. 1989 Oct 5;264(28):16537–16544. [PubMed]
  • van der Rest ME, Kamminga AH, Nakano A, Anraku Y, Poolman B, Konings WN. The plasma membrane of Saccharomyces cerevisiae: structure, function, and biogenesis. Microbiol Rev. 1995 Jun;59(2):304–322. [PMC free article] [PubMed]
  • Vestal JR, White DC. Lipid analysis in microbial ecology: quantitative approaches to the study of microbial communities. Bioscience. 1989 Sep;39(8):535–541. [PubMed]
  • Vossen RC, van Dam-Mieras MC, Hornstra G, Zwaal RF. Differential effects of endothelial cell fatty acid modification on the sensitivity of their membrane phospholipids to peroxidation. Prostaglandins Leukot Essent Fatty Acids. 1995 May;52(5):341–347. [PubMed]

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