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Disruption of mitochondrial function in Candida albicans leads to reduced cellular ergosterol levels and elevated growth in the presence of amphotericin B

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Abstract

A respiratory-deficient mutant of Candida albicans MEN was generated by culturing cells in medium supplemented with ethidium bromide at 37 °C for 5 days. The respiratory-deficient mutant (C. albicans MMU11) was incapable of growth on glycerol, had a reduced oxygen uptake rate and demonstrated an altered mitochondrial cytochrome profile. Respiratory-competent cybrids were formed by mitochondrial transfer following fusion of protoplasts with those of C. albicans ATCC 44990. Mutant MMU11 possessed lower levels of ergosterol than the parental isolates and the cybrids, and demonstrated a small but statistically significant increase in tolerance to amphotericin B. The results demonstrated that disruption of mitochondrial function in C. albicans increases the tolerance to amphotericin B, possibly mediated by a reduction in cellular ergosterol content.

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References

  • Abu-Hatab M, Whittaker PA (1992) Isolation and characterization of respiration-deficient mutants from the pathogenic yeast Candida albicans. Antonie van Leeuwenhoek 62:207–219

    Google Scholar 

  • Abu- Salah K (1996) Amphotericin B: an update. Brit J Biomed Sc 53:122–133

    Google Scholar 

  • Aoki S, Ito-Kuwa S (1987) Induction of petite mutation with acriflavine and elevated temperature in Candida albicans. J Med Vet Mycol 25:269–277

    CAS  PubMed  Google Scholar 

  • Aoki S, Ito-Kuwa S, Nakamura Y, Masuhara T (1990) Comparative pathogenicity of a wild-type strain and respiratory mutants of Candida albicans in mice. Zbl Bakt 273:332–342

    CAS  Google Scholar 

  • Arthington-Skaggs BA, Warnock DW, Morrison CJ (1999) Quantitation of ergosterol content: Novel methods for determination of fluconazole susceptibility of Candida albicans. J Clin Microbiol 37:3332–3337

    CAS  PubMed  Google Scholar 

  • Bouchara JP, Zouhair R, Le Boudouil S, Renier G, Filmon R, Chabasse D, Hallet JN, Defontaine A (2000) In vivo selection of an azole-resistance petite mutant of Candida glabrata. J Med Microbiol 49:977–984

    CAS  PubMed  Google Scholar 

  • Daum G, Lees ND, Bard M, Dickson R (1998) Biochemistry, cell biology and molecular biology of lipids of Saccharomyces cerevisiae. Yeast 14:1471–1510

    Article  CAS  PubMed  Google Scholar 

  • Defontaine A, Bouchara JP, Declerk P, Planchenault C, Chabasse D, Hallet JN (1999) In-vivo resistance to azoles associated with mitochondrial DNA deficiency in Candida glabrata. J Med Microbiol 48:663–670

    CAS  PubMed  Google Scholar 

  • Ferenczy L, Maraz A (1977) Transfer of mitochondria by protoplast fusion in Saccharomyces cerevisiae. Nature 268:524–525

    CAS  PubMed  Google Scholar 

  • Ferguson LR., Von Borstel RC (1992) Induction of the cytoplasmic petite mutation by chemical and physical agents in Saccharomyces cerevisiae. Mut Res 265:103–148

    CAS  Google Scholar 

  • Geber A, Hitchcock CA, Swartz JE, Pullen FS, Marsden KE, Kwon-Chung KJ, Bennett JE (1995) Deletion of the Candida glabrata ERG3 and ERG 11 genes: Effect on cell viability, cell growth, sterol composition and antifungal susceptibility. Antimicrob Agents Chemother 39:2708–2717

    CAS  PubMed  Google Scholar 

  • Goldering, ES, Grossman LI, Krupnick D. Cryer DR, Marmur J (1970) The petite mutation in yeast: loss of mitochondrial deoxyribonucleic acid during induction of petites with ethidium bromide. J Mol Biol 52:323–335

    PubMed  Google Scholar 

  • Gyurko C, Lendenmann U, Troxler RF, Oppenheim FG (2000) Candida albicans mutants deficient in respiration are resistant to the small cationic salivary antimicrobial peptide histatin 5. Antimicrob Agents Chemotherap 44:348–354

    Article  CAS  Google Scholar 

  • Kavanagh K, Whittaker PA (1996) Application of protoplast fusion to the non-conventional yeast. Enz Microbiol Technol 18:45–51

    Article  CAS  Google Scholar 

  • Kavanagh K, Walsh M, Whittaker PA (1991) Enhanced intraspecific protoplast fusion in yeast. FEMS Microbiol Letts 81:283–286

    Article  CAS  Google Scholar 

  • Kelly SI, Lamb DC, Kelly DE, Manning NJ, Loeffier J, Herbart H, Schumacher U, Einsele H (1997) Resistance to fluconazole and cross resistance to amphotericin B in Candida albicans from AIDS patients caused by defective sterol Δ 5,6 desaturation. FEBS Letts 400:80 −82

    Article  CAS  Google Scholar 

  • Lunel FM, Meis FG, Voss A (1999) Nosocomial fungal infections: Candidemia. Diagn Microbiol Infect Dis 34:213–220

    Article  PubMed  Google Scholar 

  • Maraz A, Ferenczy L (1980) Selective transfer of fungal cytoplasmic genetic elements by protoplast fusion. Curr Microbiol 4:343–345

    Google Scholar 

  • Moran G, Sullivan DJ, Henman MC, McCreary CE, Harrington BJ, Shanley DB, Coleman DC (1997) Anti-fungal drug susceptibilities of oral Candida dubliniensis isolates from human immunodeficiency virus (HIV)-infected and non-HIV-infected subjects and generation of stable fluconazole resistant derivatives in vitro. Antimicrob Agents Chemotherap 41:617–623

    CAS  Google Scholar 

  • Parks LW, Casey WM (1995) Physiological implications of sterol biosynthesis in yeast. Ann Rev Microbiol 49:95–116

    Article  CAS  Google Scholar 

  • Pfaller MA, Jones RN, Messer SA, Edmond MB, Wenzel RP (1998) National surveillance of nosocomial blood stream infection due to Candida albicans: frequency of occurrence and anti-fungal susceptibility in the SCOPE programme. Diagn Microbial Infect Dis 31:327–332

    Article  CAS  Google Scholar 

  • Richards MS, Van Broock MR, Figueroa LI (1987) Restoration of respiratory competence in the yeast Candida utilis after somatic fusion with Saccharomyces cerevisiae. Curr Microbiol 16:109–112

    Google Scholar 

  • Sanglard D, Ischer F, Bille J (2001) Role of ATP-binding-casette transporter genes in high frequency acquisition of resistance to azole antifungals in Candida glabrata. Antimicrob Agents Chemother 45, 1174–1183

    Google Scholar 

  • Spirek M, Horvath A, Piskur J, Sulo P (2000) Functional co-operation between the nuclei of Saccharomyces cerevisiae and the mitochondria from other yeast species. Curr Genet 38:202–207

    Article  CAS  PubMed  Google Scholar 

  • Vazquez JA, Arganoza MT, Vaishampayan JK, Akins RA (1996) In vitro interaction between Amphotercin B and azoles in Candida albicans. Antimicrob Agents Chemother 40:2511–2516

    CAS  PubMed  Google Scholar 

  • White TC, Marr KA, Bowden RA (1998) Clinical, cellular and molecular factors that contribute to antifungal drug resistance. Clin Microbiol Rev 11:382–402

    CAS  PubMed  Google Scholar 

  • Whittaker PA, Danks SM (1978) Mitochondria: structure, function and assembly. Integrated Themes in Biology, Longman, London

    Google Scholar 

  • Wolfger H, Mamnun YM, Kuchler K (2001) Fungal ABC proteins: pleiotropic drug resistance, stress response and cellular detoxification. Res Microbiol 152: 375–389

    Google Scholar 

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Acknowledgements

The authors are grateful to Bernie Coleman and Donal O'Shea for assistance with GC analysis. Patrick Geraghty is the recipient of a grant from the Irish American Partnership. This work was supported by funding to the National Institute for Cellular Biotechnology under PRTLI 3.

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Correspondence to Kevin Kavanagh.

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Geraghty, P., Kavanagh, K. Disruption of mitochondrial function in Candida albicans leads to reduced cellular ergosterol levels and elevated growth in the presence of amphotericin B. Arch Microbiol 179, 295–300 (2003). https://doi.org/10.1007/s00203-003-0530-y

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  • DOI: https://doi.org/10.1007/s00203-003-0530-y

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