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Phenotypic Switching of Candida guilliermondii is Associated with Pseudohyphae Formation and Antifungal Resistance

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Abstract

Switching between two cell types in fungi is called phenotypic switching, and it is commonly observed in pathogenic yeast. Candida lusitaniae undergoes antifungal resistance-associated phenotypic switching and results in three colony colors: light brown, brown and dark brown. In this study, we included C. lusitaniae as control. This study had two objectives. First, we wanted to evaluate whether also a prevalent human pathogen C. guilliermondii can undergo phenotypic switching. Second, our aim was to determine whether switching can change yeasts susceptibility to antifungals. Yeast suspension (1 × 103–5 × 103 c.f.u./ml) was plated on the YPD medium containing 1 mM CuSO4. Colonies exhibiting the original and variant phenotypes were counted and converted to percentage of the population. Minimum inhibitory concentrations of amphotericin B, formic acid and acetic acid for the cells from random colonies of the different phenotypes were determined by microdilution method. After 5 days of incubation, C. guilliermondii switched spontaneously and reversibly among two phenotypes distinguishable on CuSO4 containing agar, white and dark brown. Phenotypes occurred with greater frequency (10−1–10−2) than spontaneous mutations and were reversible, fulfilling the two phenotypic switching criteria. The study showed that phenotypic switching was associated with filamentation and affected antifungal resistance. Resistance to amphotericin B increased tenfold and was associated with C. lusitaniae dark brown phenotype. C. guilliermondii colonies with brown phenotype displayed 20 and 2 times higher resistance to amphotericin B and acetic acid, respectively.

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References

  1. Pfaller MA, Diekema DJ. Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev. 2007;20:133–63.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Pemán J, Salavert M. General epidemiology of invasive fungal disease. Enferm Infecc Microbiol Clin. 2012;30:90–8.

    Article  PubMed  Google Scholar 

  3. van der Woude MW. Re-examining the role and random nature of phase variation. FEMS Microbiol Lett. 2006;254:190–7.

    Article  PubMed  Google Scholar 

  4. Jain N, Hasan F, Fries BC. Phenotypic switching in fungi. Curr Fungal Infect Rep. 2008;2:180–8.

    Article  PubMed Central  PubMed  Google Scholar 

  5. Soll DR. Candida commensalism and virulence: the evolution of phenotypic plasticity. Acta Trop. 2002;81:101–10.

    Article  PubMed  Google Scholar 

  6. Kolotila MP, Diamond RD. Effects of neutrophils and in vitro oxidants on survival and phenotypic switching of Candida albicans WO-1. Infect Immun. 1990;58:1174–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  7. Lan CY, Newport G, Murillo LA, Jones T, Scherer S, Davis RW, Agabian N. Metabolic specialization associated with phenotypic switching in Candida albicans. Proc Natl Acad Sci USA. 2002;99:14907–12.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Favela A, Michel-Nguyenb A, Peyron F, Martin C, Thomachot L, Datry A, Bouchara JP, Challier S, Noel T, et al. 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. Diagn Microbiol Infect Dis. 2003;47:331–9.

    Article  Google Scholar 

  9. Pfaller MA. Antifungal drug resistance: mechanisms, epidemiology, and consequences for treatment. Am J Med. 2012;125(Suppl. 1):3–13.

    Article  Google Scholar 

  10. Slutsky B, Staebell M, Anderson J, Risen L, Pfaller M, Soll DR. “White-opaque transition”: a second high-frequency switching system in Candida albicans. J Bacteriol. 1987;169:189–97.

    PubMed Central  CAS  PubMed  Google Scholar 

  11. Pujol C, Daniels KJ, Lockhart SR, Srikantha T, Radke JB, Geiger J, Soll DR. The closely related species Candida albicans and Candida dubliniensis can mate. Eukaryot Cell. 2004;3:1015–27.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Porman AM, Alby K, Hirakawa MP, Bennett RJ. Discovery of a phenotypic switch regulating sexual mating in the opportunistic fungal pathogen Candida tropicalis. Proc Natl Acad Sci USA. 2011;108:21158–63.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Lachke SA, Joly S, Daniels KJ, Soll DR. Phenotypic switching and filamentation in Candida glabrata. Microbiology. 2002;148:2661–74.

    CAS  PubMed  Google Scholar 

  14. Brockert PJ, Lachke SA, Srikantha T, Pujol C, Galask R, Soll DR. Phenotypic switching and mating type switching of Candida glabrata at sites of colonization. Infect Immun. 2003;71:7109–18.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Miller NS, Dick JD, Merz WG. Phenotypic switching in Candida lusitaniae on copper sulfate indicator agar: association with amphotericin B resistance and filamentation. J Clin Microbiol. 2006;44:1536–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Lastauskienė E, Zinkevičienė A, Girkontaitė I, Kaunietis A, Kvedarienė V. Formic acid and acetic acid induce a programmed cell death in pathogenic Candida species. Curr Microbiol. 2014;69:303–10.

    Article  PubMed  Google Scholar 

  17. Zinkevičienė A, Vaičiulionienė N, Baranauskienė I, Kvedarienė V, Ėmužytė R, Čitavičius D. Cutaneous yeast microflora in patients with atopic dermatitis. Cent Eur J Med. 2011;6:713–9.

    Article  Google Scholar 

  18. Lachke SA, Srikantha T, Tsai LK, Daniels K, Soll DR. Phenotypic switching in Candida glabrata involves phase-specific regulation of the metallothionein gene MT-11 and the newly discovered hemolysin gene HLP. Infect Immun. 2000;68:884–95.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Williamson EM. Synergy and other interactions in phytomedicines. Phytomedicine. 2001;8:401–9.

    Article  CAS  PubMed  Google Scholar 

  20. Thompson DS, Carlisle PL, Kadosh D. Coevolution of morphology and virulence in Candida spiecies. Eukaryot Cell. 2011;10:1173–82.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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

    PubMed Central  PubMed  Google Scholar 

  22. Lo HJ, Köhler JR, DiDomenico D, Loebenberg D, Cacciapuoti A, Fink GR. Nonfilamentous C. albicans mutants are avirulent. Cell. 1997;90:939–49.

    Article  CAS  PubMed  Google Scholar 

  23. Pfaller MA, Diekema DJ, Mendez M, Kibbler C, Erzsebet P, Chang SC, Gibbs DL, Newell VA, The Global Antifungal Surveillance Group Candida guilliermondii. An opportunistic fungal pathogen with decreased susceptibility to fluconazole: geographic and temporal trends from the ARTEMIS DISK antifungal surveillance program. J Clin Microbiol. 2006;44:3551–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Pfaller MA, Diekema DJ, Messer SA, Boyken L, Hollis RJ, Jones RN. In vitro susceptibilities of rare Candida bloodstream isolates to ravuconazole and three comparative antifungal agents. Diagn Microbiol Infect Dis. 2004;48:101–5.

    Article  CAS  PubMed  Google Scholar 

  25. Vargas K, Messer SA, Pfaller M, Lockhart SR, Stapleton JT, Hellstein J, Soll DR. Elevated phenotypic switching and drug resistance of Candida albicans from human immunodeficiency virus-positive individuals prior to first thrush episode. J Clin Microbiol. 2000;38:3595–607.

    PubMed Central  CAS  PubMed  Google Scholar 

  26. Yoon SA, Vazques JA, Steffan PE, Sobel JD, Akins RA. High-frequency, in vitro reversible switching of Candida lusitaniae clinical isolates from amphotericin B susceptibility to resistance. Antimicrob Agents Chemother. 1999;43:836–45.

    PubMed Central  CAS  PubMed  Google Scholar 

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Microbiology and Biotechnology, Faculty of Natural Sciences, Vilnius University, M.K. Čiurlionio Str. 21/27, 3101, Vilnius, Lithuania

    Eglė Lastauskienė & Jolita Čeputytė

  2. Department of Immunology, State Research Institute Centre for Innovative Medicine, Žygimantų str. 9, 01102, Vilnius, Lithuania

    Irutė Girkontaitė & Auksė Zinkevičienė

Authors
  1. Eglė Lastauskienė
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  2. Jolita Čeputytė
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  3. Irutė Girkontaitė
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  4. Auksė Zinkevičienė
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Correspondence to Auksė Zinkevičienė.

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Lastauskienė, E., Čeputytė, J., Girkontaitė, I. et al. Phenotypic Switching of Candida guilliermondii is Associated with Pseudohyphae Formation and Antifungal Resistance. Mycopathologia 179, 205–211 (2015). https://doi.org/10.1007/s11046-014-9844-3

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  • DOI: https://doi.org/10.1007/s11046-014-9844-3

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