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Formic Acid and Acetic Acid Induce a Programmed Cell Death in Pathogenic Candida Species

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Abstract

Cutaneous fungal infections are common and widespread. Antifungal agents used for the treatment of these infections often have undesirable side effects. Furthermore, increased resistance of the microorganisms to the antifungal drugs becomes the growing problem. Accordingly, the search for natural antifungal compounds continues to receive attention. Apoptosis is highly regulated programmed cell death. During yeast cell apoptosis, amino acids and peptides are released and can stimulate regeneration of human epithelium cells. Thus, detection of chemical compounds inducing apoptosis in yeast and nontoxic for humans is of great medical relevance. The aim of this study was to detect chemical compound inducing apoptosis in pathogenic Candida species with the lowest toxicity to the mammalian cells. Five chemical compounds—acetic acid, sodium bicarbonate, potassium carbonate, lithium acetate, and formic acid—were tested for evaluation of antifungal activity on C. albicans, C. guilliermondii, and C. lusitaniae. The results showed that acetic acid and formic acid at the lowest concentrations induced yeast cells death. Apoptosis analysis revealed that cells death was accompanied by activation of caspase. Minimal inhibitory concentrations of potassium carbonate and sodium bicarbonate induced Candida cells necrosis. Toxicity test with mammalian cell cultures showed that formic acid has the lowest effect on the growth of Jurkat and NIH 3T3 cells. In conclusion, our results show that a low concentration of formic acid induces apoptosis-like programmed cell death in the Candida yeast and has a minimal effect on the survivability of mammalian cells, suggesting potential applications in the treatment of these infections.

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References

  1. Arslan U, Ilhan K, Vardar C, Karabulut OA (2009) Evaluation of antifungal activity of food additives against soil borne phytopathogenic fungi. World J Microbiol Biotech 25:537–543

    Article  CAS  Google Scholar 

  2. Baimark Y, Threeprom J, Dumrongchai N, Srisuwan Y, Kotsaeng N (2008) Utilization of wood vinegars as sustainable coagulating and antifungal agents in the production of natural rubber sheets. J Environ Sci Technol 1:157–163

    Article  CAS  Google Scholar 

  3. Banuelos MA, Sychrova H, Bleykasten-Grosshans C, Souciet JL, Potier S (1998) The Nha1 antiporter of Saccharomyces cerevisiae mediates sodium and potassium efflux. Microbiology 144:2749–2758

    Article  CAS  PubMed  Google Scholar 

  4. Bjornsdottir K, BreidtJr F, McFeeters RF (2006) Protective effects of organic acids on survival of Escherichia coli O157: H7 in acidic environments. Appl Environ Microbiol 72:660–664

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Bidra AS, Tarrand JJ, Roberts DB, Rolston KV, Chambers MS (2011) Antimicrobial efficacy of oral topical agents on microorganisms associated with radiated head and neck cancer patients: an in vitro study. Quintessence Int 42:307–315

    PubMed  Google Scholar 

  6. Brand A (2012) Hyphal growth in human fungal pathogens and its role in virulence. Int J Microbiol. doi:10.1155/2012/517529

    PubMed Central  PubMed  Google Scholar 

  7. Buttner S, Eisenberg T, Carmona-Gutierrez D, Ruli D, Knauer H, Ruckenstuhl C, Sigrist C, Wissing S, Kollroser M, Frohlich KU, Sigrist S, Madeo F (2007) Endonuclease G regulates budding yeast life and death. Mol Cell 25:233–246

    Article  PubMed  Google Scholar 

  8. Clinical and Laboratory Standard Institute (2008) Reference method for broth dilution antifungal susceptibility testing of yeasts; approved standard-third edition; CLSI document M27-A3. CLSI, Wayne

    Google Scholar 

  9. Du L, Su Y, Sun D, Zhu W, Wang J, Zhuang X, Zhou S, Lu Y (2008) Formic acid induces Yca1p-independent apoptosis-like cell death in the yeast Saccharomyces cerevisiae. FEMS Yeast Res 8:531–539

    Article  CAS  PubMed  Google Scholar 

  10. EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) (2012) Scientific opinion on the safety and efficacy of acetic acid, sodium diacetate and calcium acetate as preservatives for feed for all animal species. EFSA J 10:2571

    Google Scholar 

  11. Favel A, Michel-Nguyen A, Peyron F, Martin C, Thomachot L, Datry A, Bouchara JP, Challier S, Noël T, Chastin C, Regli P (2003) Colony morphology switching of Candida lusitaniae and acquisition of multidrug resistance during treatment of a renal infection in a newborn: case report and review of the literature. Diagnmicrobiol Infect Dis 47:331–339

    Article  Google Scholar 

  12. Hawkins JL, Baddour LM (2003) Candida lusitaniae infections in the era of fluconazole availability. Clin Infect Dis 36:14–18

    Article  Google Scholar 

  13. Huang CB, Alimova Y, Myers TM, Ebersole JL (2011) Short- and medium-chain fatty acids exhibit antimicrobial activity for oral microorganisms. Arch Oral Biol 56:650–654

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. In YW, Kim JJ, Kim HJ, Oh SW (2013) Antimicrobial activities of acetic acid, citric acid and lactic acid against Shigella species. J Food Safety 33:79–85

    Article  Google Scholar 

  15. Krauke Y, Sychrova H (2010) Four pathogenic Candida species differ in salt tolerance. Curr Microbiol 61:335–339

    Article  CAS  PubMed  Google Scholar 

  16. Letscher-Bru V, Obszynski CM, Samsoen M, Sabou M, Waller J, Candolfi E (2013) Antifungal activity of sodium bicarbonate against fungal agents causing superficial infections. Mycopathologia 175:153–158

    Article  CAS  PubMed  Google Scholar 

  17. Lo HJ, Köhler JR, DiDomenico B, Loebenberg D, Cacciapuoti A, Fink GR (1997) Nonfilamentous C. albicans mutants are avirulent. Cell 90:939–949

    Article  CAS  PubMed  Google Scholar 

  18. Ludovico P, Sousa MJ, Silva MT, Leao C, Corte-Real M (2001) Saccharomyces cerevisiae commits to a programmed cell death process in response to acetic acid. Microbiology 147:2409–2415

    CAS  PubMed  Google Scholar 

  19. Madeo F, Frohlich E, Frohlich KU (1997) A yeast mutant showing diagnostic markers of early and late apoptosis. J Cell Biol 139:729–734

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Malik YS, Goyal SM (2006) Virucidal efficacy of sodium bicarbonate on a food contact surface against feline calicivirus, a norovirus surrogate. Int J Food Microbiol 109:160–163

    Article  CAS  PubMed  Google Scholar 

  21. Miller NS, Dick JD, Merz WG (2006) Phenotypic switching in Candida lusitaniae on copper sulfate indicator agar: association with amphotericin B resistance and filamentation. J Clin Microbiol 44:1536–1539

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Mollapour M, Piper PW (2007) Hog1 mitogen-activated protein kinase phosphorylation targets the yeast Fps1 aquaglyceroporin for endocytosis, thereby rendering cells resistant to acetic acid. Mol Cell Biol 27:6446–6456

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Palmer CL, Horst RK, Langhans RW (1997) Use of bicarbonates to inhibit in vitro colony growth of Botrytis cinerea. Plant Dis 81:1432–1438

    Article  Google Scholar 

  24. Patel M, Shackleton JA, Coogan MM, Galpin J (2008) Antifungal effect of mouth rinses on oral Candida counts and salivary flow in treatment—naive HIV-infected patients. AIDS Patient Care STDS 22:613–618

    Article  PubMed  Google Scholar 

  25. Plumed-Ferrer C, von Wright A (2011) Antimicrobial activity of weak acids in liquid feed fermentations, and its effects on yeasts and lactic acid bacteria. J Sci Food Agric 91:1032–1040

    Article  CAS  PubMed  Google Scholar 

  26. Raftari M, AziziJalilian F, Abdulamir AS, Son R, Sekawi Z, Fatimah AB (2009) Effect of organic acids on Escherichia coli O157:H7 and Staphylococcus aureus contaminated meat. Open Microbiol J 3:121–127

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Rodriguez-Urra AB, Jimenez C, Duenas M, Ugalde U (2009) Bicarbonate gradients modulate growth and colony morphology in Aspergillus nidulans. FEMS Microbiol Lett 300:216–221

    Article  CAS  PubMed  Google Scholar 

  28. Ryssel H, Kloeters O, Germann G, Schäfer T, Wiedemann G, Oehlbauer M (2009) The antimicrobial effect of acetic acid–an alternative to common local antiseptics? Burns 35:695–700

    Article  CAS  PubMed  Google Scholar 

  29. Silici S, Koc AN (2006) Comparative study of in vitro methods to analyse the antifungal activity of propolis against yeasts isolated from patients with superficial mycoses. Lett Appl Microbiol 43:318–324

    Article  CAS  PubMed  Google Scholar 

  30. Watanabe H, Azuma M, Igarashi K, Ooshima H (2006) Relationship between cell morphology and intracellular potassium concentration in Candida albicans. J Antibiot (Tokyo) 59:281–287

    Article  CAS  Google Scholar 

  31. Willamil J, Creus E, Pérez JF, Mateu E, Martin-Orúe SM (2011) Effect of a microencapsulated feed additive of lactic and formic acid on the prevalence of Salmonella in pigs arriving at the abattoir. Arch Anim Nutr 65:431–444

    Article  CAS  PubMed  Google Scholar 

  32. Zinkevičienė A, Vaičiulionienė N, Baranauskienė I, Kvedarienė V, Ėmužytė R, Čitavičius D (2011) Cutaneous yeast microflora in patients with atopic dermatitis. Cent Eur J Med 6:713–719

    Article  Google Scholar 

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Correspondence to Auksė Zinkevičienė.

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Lastauskienė, E., Zinkevičienė, A., Girkontaitė, I. et al. Formic Acid and Acetic Acid Induce a Programmed Cell Death in Pathogenic Candida Species. Curr Microbiol 69, 303–310 (2014). https://doi.org/10.1007/s00284-014-0585-9

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  • DOI: https://doi.org/10.1007/s00284-014-0585-9

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