Skip to main content
SpringerLink
Log in

Antifungal activity of alkanols: inhibition of growth of spoilage yeasts

  • Published:
Phytochemistry Reviews Aims and scope Submit manuscript

Abstract

Primary aliphatic alkanols from C6 to C13 were tested for their antifungal activity against Saccharomyces cerevisiae using a broth dilution method. Undecanol (C11) was found to be the most potent fungicide against this yeast with the minimum fungicidal concentration (MFC) of 25 μg/ml (0.14 mM), followed by decanol (C10) with the minimum inhibitory concentration (MIC) of 50 μg/ml (0.31 mM). The time-kill curve study showed that undecanol was fungicidal against S. cerevisiae at any growth stages. This fungicidal activity was not influenced by pH values. Dodecanol (C12) was the most effective fungistatic but did not show any fungicidal activity up to 1600 μg/mL. Fungistatic dodecanol quickly reduced cell viability, but the cell viability recovered shortly after and then finally became no longer different from the control indicating that the effect of dodecanol on S. cerevisiae was classified as a sublethal damage. However, fungistatic dodecanol combined with sublethal amount of anethole showed a fungicidal activity against this yeast. Anethole completely restricted the recovery of cell viability. Therefore expression of the synergistic effect was probably due to the blockade of the recovering process from dodecanol induced-stress. The alkanols tested inhibited glucose-induced acidification by inhibiting the plasma membrane H+-ATPase. Octanol (C8) increased plasma membrane fluidity in the spheroplast cells of S. cerevisiae. The same series of aliphatic primary alkanols was also tested against a food spoilage fungus Zygosaccharomyces bailii and compared with their effects against S. cerevisiae. Decanol was found to be the most potent fungicide against Z. bailii with an MFC of 50 μg/ml (0.31 mM), whereas undecanol was found to be the most potent fungistatic with an MIC of 25 μg/ml (0.14 mM). The time-kill curve study showed that decanol was fungicidal against Z. bailii at any growth stage. This antifungal activity was slightly enhanced in combination with anethole. The primary antifungal action of medium-chain (C9–C12) alkanols comes from their ability as nonionic surfactants to disrupt the native membrane-associated function of the integral proteins. Hence, the antifungal activity of alkanols is mediated by biophysical process, and the maximum activity can be obtained when balance between hydrophilic and hydrophobic portions becomes the most appropriate.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13
Fig. 14

Similar content being viewed by others

References

  • Alexandre H, Mathieu B, Charpentier C (1996) Alteration in membrane fluidity and lipid composition, and modulation of H+-ATPase activity in Saccharomyces cerevisiae caused by decanoic acid. Microbiology 142:469–475

    Article  PubMed  CAS  Google Scholar 

  • Brockerhoff H (1974) Model of interaction of polar lipids, cholesterol, and proteins in biological membranes. Lipids 9:645–650

    Article  PubMed  CAS  Google Scholar 

  • Chauhan VPS, Ramsammy LS, Brockerhoff H (1984) Molecular interactions in the hydrogen belts of membranes glucose-6-phosphate, lysophosphatidylcholine, and cholesterol. Biochim Biophys Acta 772:239–243

    Article  PubMed  CAS  Google Scholar 

  • Chiou JS, Ma SM, Kamaya H, Ueda I (1990) Anesthesia cutoff phenomenon: interfacial hydrogen bonding. Science 248:583–585

    Article  PubMed  CAS  Google Scholar 

  • Coote PJ, Jones MV, Seymour IJ, Rowe DL, Ferdinando DP, McArthur AJ, Cole MB (1994) Activity of the plasma membrane H+-ATPase is a key physiological determinant of thermotolerance in Saccharomyces cerevisiae. Microbiology 140(8):1881–1890

    Article  PubMed  CAS  Google Scholar 

  • Deak T, Beuchat LR (1994) Use of indirect conductimetry to predict the growth of spoilage yeasts, with special consideration of Zygosaccharomyces bailii. Int J Food Microbiol 23:405–417

    Article  PubMed  CAS  Google Scholar 

  • Edelfors S, Ravn-Jonsen AA (1990) The effects of alcohols in vitro on the nervous cell membrane measured by changes in the (Ca2+/Mg2+) ATPase activity and fluidity of the synaptosomal membrane. Pharmacol Toxicol 67:56–60

    Article  PubMed  CAS  Google Scholar 

  • Eliasz AW, Warth AD (1976) Transport of benzoic and propanoic acids by Zygosaccharomyces bailii. J General Microbiol 135:1383–1390

    Google Scholar 

  • Elliott JR, Haydon DA (1989) The actions of neutral anesthetics on ion conductances of nerve membranes. Biochim Biophys Acta 988:257–286

    Article  PubMed  CAS  Google Scholar 

  • Evans IH (1983) Molecular genetic aspects of yeast mitochondria. In: Spencer JFT, Spencer DM, Smith ARW (eds) Yeast genetics. Fundamental and applied aspects. Springer, New York, pp 269–370

    Chapter  Google Scholar 

  • Fleet G (1992) Spoilage yeasts. Crit Rev Biotechnol 12:1–44

    Article  PubMed  CAS  Google Scholar 

  • Franks NP, Lieb WR (1986) Partitioning of long-chain alcohols into lipid bilayers: implications for mechanisms of general anesthesia. Proc Natl Acad Sci USA 83:5116–5120

    Article  PubMed  CAS  Google Scholar 

  • Fujita K, Kubo I (2002) Membrane injury by nonyl gallate, plasma membrane injury induced by nonyl gallate in Saccharomyces cerevisiae. J Appl Microbiol 92:1035–1042

    Article  PubMed  CAS  Google Scholar 

  • Fujita K, Kubo I (2004) Potentiation of fungicidal activities of trans-anethole against Saccharomyces cerevisiae under hypoxic condition. J Biosci Bioeng 98:490–492

    PubMed  CAS  Google Scholar 

  • Fujita K, Kubo I (2005a) Multifunctional action of antifungal polygodial against Saccharomyces cerevisiae: involvement of pyrrole formation on cell surface in antifungal action. Bioorg Med Chem 13:6742–6747

    Article  PubMed  CAS  Google Scholar 

  • Fujita K, Kubo I (2005b) Naturally occurring antifungal agents against Zygosaccharomyces bailii and their synergism. J Agric Food Chem 53:5187–5191

    Article  PubMed  CAS  Google Scholar 

  • Fujita K, Fujita T, Kubo I (2008) Antifungal activity of alkanols against Zygosaccharomyces bailii and their effects on plasma membrane. Phytother Res 22:1349–1355

    Article  PubMed  CAS  Google Scholar 

  • Hammond DG, Kubo I (2000) Alkanols inhibit respiration of intact mitochondria and display cutoff similar to that measured in vivo. J Pharm Exp Therap 293:822–828

    CAS  Google Scholar 

  • Hansch C, Dunn WJ III (1972) Linear relationships between lipophilic character and biological activity of drugs. J Pharm Sci 61:1–19

    Article  PubMed  CAS  Google Scholar 

  • Hasinoff BB, Davey JP (1989) The inhibition of a membrane-bound enzyme as a model for anesthetic action and drug toxicity. Biochem J 258:101–107

    PubMed  CAS  Google Scholar 

  • Haydon DA, Urban BW (1983) The action of alcohols and other non-ionic surface active substances on the sodium current of the squid giant axon. J Physiol 341:411–427

    PubMed  CAS  Google Scholar 

  • Himejima M, Kubo I (1993) Fungicidal activity of polygodial in combination with anethole and indole against Candida albicans. J Agric Food Chem 41(10):1776–1779

    Article  CAS  Google Scholar 

  • Hitokoto H, Morozumi S, Wauke T, Sakai S, Kurata H (1980) Inhibitory effects of spices on growth and toxin production of toxigenic fungi. Appl Environ Microbiol 39:818–822

    PubMed  CAS  Google Scholar 

  • Holyoak CD, Stratford M, McMullin Z, Cole MB, Crimmins K, Brown AJP, Coote PJ (1996) Activity of the plasma membrane H+-ATPase and optimal glycolytic flux are required for rapid adaptation and growth of Saccharomyces cerevisiae in the presence of the weak-acid preservative sorbic acid. Appl Environ Microbiol 62:3158–3164

    PubMed  CAS  Google Scholar 

  • Janoff AS, Pringle MJ, Miller KW (1981) Correlation of anesthetic potency with solubility in membranes. Biochim Biophys Acta 649:125–128

    Article  PubMed  CAS  Google Scholar 

  • Kalathenos P, Sutherland JP, Roberts TA (1995) Resistance of some wine spoilage yeasts to combines of ethanol and acids present in wine. J Appl Bacterial 78:245–250

    Article  CAS  Google Scholar 

  • Kubo I, Himejima M (1991) Anethole, a synergist of polygodial against filamentous microorganisms. J Agric Food Chem 39:2290–2292

    Article  CAS  Google Scholar 

  • Kubo I, Himejima M (1992) Potentiation of antifungal activity of sesquiterpene dialdehydes against Candida albicans and two other fungi. Experientia 48:1162–1164

    Article  PubMed  CAS  Google Scholar 

  • Kubo A, Kubo I (1995) Antimicrobial agents from Tanacetum balsamita. J Nat Prod 58:1565–1569

    Article  CAS  Google Scholar 

  • Kubo I, Lee SH (1998) Potentiation of antifungal activity of sorbic acid. J Agric Food Chem 46:4052–4055

    Article  CAS  Google Scholar 

  • Kubo I, Himejima M, Muroi H (1993) Combination effects of antifungal nagilactones against Candida albicans and two other fungi with phenylpropanoids. J Nat Prod 56:220–226

    Article  PubMed  CAS  Google Scholar 

  • Kubo I, Muroi H, Himejima M, Kubo A (1995) Structural functions of antimicrobial long-chain alcohols and phenols. Bioorg Med Chem 3:873–880

    Article  PubMed  CAS  Google Scholar 

  • Kubo I, Fujita K, Lee SH (2001) Antifungal mechanism of polygodial. J Agric Food Chem 49:1607–1611

    Article  PubMed  CAS  Google Scholar 

  • Kubo I, Fujita T, Kubo A, Fujita K (2003) Modes of antifungal action of alkanols against Saccharomyces cerevisiae. Bioorg Med Chem 11:1117–1122

    Article  PubMed  CAS  Google Scholar 

  • Machida K, Tanaka T, Fujita K, Taniguchi M (1998) Farnesol-induced generation of reactive oxygen species via indirect inhibition of the mitochondrial electron transport chain in the yeast Saccharomyces cerevisiae. J Bacteriol 180:4460–4465

    PubMed  CAS  Google Scholar 

  • Makkar RS, Cameotra SS (2002) An update on the use of unconventional substrates for biosurfactant production and their new applications. Appl Microbiol Biotechnol 58:428–434

    Article  PubMed  CAS  Google Scholar 

  • Martorell P, Stratford M, Steels H, Fernandez-Espinar MT, Querol A (2007) Physiological characterization of spoilage strains of Zygosaccharomyces bailii and Zygosacharomyces rouxii isolated from high sugar environments. Int J Food Microbiol 114:234–243

    Article  PubMed  CAS  Google Scholar 

  • Miller KW, Firestone LL, Alifimoff JK, Streicher P (1989) Nonanethetic alcohols dissolve in synaptic membranes without perturbing their lipids. Proc Natl Acad Sci USA 86:1084–1087

    Article  PubMed  CAS  Google Scholar 

  • Neves L, Pampulha ME, Loureiro-Dias MC (1994) Resistance of food spoilage to sorbic acid. Lett Appl Microbiol 19:8–11

    Article  CAS  Google Scholar 

  • Nikaido H (1994) Prevention of drug access to bacterial targets: permeability barriers and active efflux. Science 264:383–388

    Article  Google Scholar 

  • Oh HI, Kim YJ, Chang EJ, Kim JY (2001) Antimicrobial characteristics of chitosan against food spoilage microorganisms in liquid media and mayonnaise. Biosci Biotechnol Biochem 65(11):2378–2383

    Article  PubMed  CAS  Google Scholar 

  • Peoples RW, Li C, Weight FF (1996) Lipid vs protein theories of alcohol action in the nervous system. Annu Rev Pharmacol Toxicol 36:185–201

    Article  PubMed  CAS  Google Scholar 

  • Petrov VV, Slayman CW (1995) Site-directed mutagenesis of the yeast pma1 H+-ATPase. J Biol Chem 270:28535–28540

    Article  PubMed  CAS  Google Scholar 

  • Sallee VL (1978) Fatty acid and alcohol partitioning with intestinal brush border and erythrocyte membranes. J Membr Biol 43:187–201

    Article  PubMed  CAS  Google Scholar 

  • Schreier Sh, Malheiros SVP, de Paula E (2000) Surface active drugs: self-association amd interaction with membranes and surfactants. Physicochemical and biological aspects. BBA-Biomembranes 1508:210–234

    Article  PubMed  CAS  Google Scholar 

  • Serrano R, Kielland-Brandt MC, Fink GR (1986) Yeast plasma membrane ATPase is essential for growth and has homology with sodium-potassium, potassium, and calcium ATPases. Nature 319:689–693

    Article  PubMed  CAS  Google Scholar 

  • Smittle RB (1977) Microbiology of mayonnaise and salad dressing: a review. J Food Protect 40:415–422

    CAS  Google Scholar 

  • Smittle RB, Flowers RS (1982) Acid tolerant microorganisms involved in the spoilage of salad dressings. J Food Protect 45:977–983

    Google Scholar 

  • Sofos JN, Busta FF (1983) Sorbates. In: Branen AL, Davidson PM (eds) Antimicrobials in food. Dekker, New York, pp 141–175

    Google Scholar 

  • Sousa MJ, Rodrigues F, Côrte-Real M, Leão C (1998) Mechanism underlying the transport and intracellular metabolism of acetic acid in the presence of glucose in the yeast Zygosaccharomyces bailii. Microbiology 144:665–670

    Article  PubMed  CAS  Google Scholar 

  • Steels H, James SA, Roberts IN, Stratford M (2000) Sorbic acid resistance: the innocuous effect. Yeast 16:1173–1183

    Article  PubMed  CAS  Google Scholar 

  • Sugie C, Shibamoto Y, Ito M, Ogino H, Miyamoto A, Fukaya N, Niimi H, Hashizume T (2006) Radiobiologic effect of intermittent radiation exposure in murine tumors. Int J Radiat Oncol Biol Phys 64:619–624

    Article  PubMed  Google Scholar 

  • Tani K, Usuki Y, Motoba K, Fujita K, Taniguchi M (2002) UK-2A, B, C, and D, novel antifungal antibiotics from Streptomyces sp. 517-02 VII. Membrane injury induced by C9-UK-2A, a derivative of UK-2A, in Rhodotorula mucilaginosa IFO 0001. J Antibiot 55:315–321

    Article  PubMed  CAS  Google Scholar 

  • Thomas DS, Davenport R (1985) Zygosaccharomyces bailii: a profile of characteristics and spoilage activities. Food Microbiol 2:157–169

    Article  Google Scholar 

  • Treistman SN, Wilson A (1987) Alkanol effects on early potassium currents in aplysia neurons depend on chain length. Proc Natl Acad Sci USA Neurobiol 84:9299–9303

    Article  CAS  Google Scholar 

  • Trombetta D, Saija A, Bisignano G, Arena S, Caruso S, Mazzanti G, Uccella N, Castelli F (2002) Study on the mechanisms of the antibacterial action of some plant αβ-unsaturated aldehydes. Lett Appl Microbiol 35:285–290

    Article  PubMed  CAS  Google Scholar 

  • Walsh SE, Maillard J-Y, Rusell AD, Catrenich CE, Charbonneau DC, Bartolo RG (2003) Activity and mechanisms of action of selected biocidal agents on Gram-positive and—negative bacteria. J Applied Microbiol 94(2):240–247

    Article  CAS  Google Scholar 

  • Warth AD (1977) Mechanism of resistance of Saccharomyces bailii to benzoic, sorbic and other weak acids used as food preservatives. J Appl Bacteriol 43:215–230

    Article  CAS  Google Scholar 

  • Warth AD (1991) Mechanism of action of benzoic acid on Zygosaccharomyces bailii: effects on glycolytic metabolite levels, energy production, and intracellular pH. Appl Environ Microbiol 57:3410–3414

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors are indebted to Drs. K. Fujita, A. Kubo, S. H. Lee, H. Muroi, and M. Himejima for performing antimicrobial assay in part. CLC is grateful to CONICYT Chile through FONDECYT Program, Grants 1101003 and 1130242 for financial support in part.

Author information

Authors and Affiliations

  1. Department of Environmental Science, Policy and Management, University of California, Berkeley, CA, 94720-3114, USA

    Isao Kubo

  2. Basic Science Department, Faculty of Sciences, University of Bio Bio, P.O. Box 447, 8700000, Chillan, Ñuble, Chile

    Carlos L. Cespedes

Authors
  1. Isao Kubo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carlos L. Cespedes
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Isao Kubo or Carlos L. Cespedes.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kubo, I., Cespedes, C.L. Antifungal activity of alkanols: inhibition of growth of spoilage yeasts. Phytochem Rev 12, 961–977 (2013). https://doi.org/10.1007/s11101-013-9325-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11101-013-9325-1

Keywords

Search

Navigation