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Ketoconazole inhibits Malassezia furfur morphogenesis in vitro under filamentation optimized conditions

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Abstract

Malassezia furfur, a constituent of the normal human skin flora, is an etiological agent of pityriasis versicolor, which represents one of the most common human skin diseases. Under certain conditions, both exogenous and endogenous, the fungus can transition from a yeast form to a pathogenic mycelial form. To develop a standardized medium for reproducible production of the mycelial form of M. furfur to develop and optimize susceptibility testing for this pathogen, we examined and characterized variables, including kojic acid and glycine concentration, agar percentage, and pH, to generate a chemically defined minimal medium on which specific inoculums of M. furfur generated the most robust filamentation. Next, we examined the capacity of ketoconazole to inhibit the formation of M. furfur mycelial form. Both low and high, 0.01, 0.05 and 0.1 µg/ml concentrations of ketoconazole significantly inhibited filamentation at 11.9, 54.5 and 86.7%, respectively. Although ketoconazole can have a direct antifungal effect on both M. furfur yeast and mycelial cells, ketoconazole also has a dramatic impact on suppressing morphogenesis. Since mycelia typified the pathogenic form of Malassezia infection, the capacity of ketoconazole to block morphogenesis may represent an additional important effect of the antifungal.

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References

  1. Barchmann T, Hort W, Krämer HJ, Mayser P (2011) Glycine as a regulator of tryptophan-dependent pigment synthesis in Malassezia furfur. Mycoses 54(1):17–22

    Article  CAS  PubMed  Google Scholar 

  2. Borelli D, Jacobs PH, Nall L (1991) Tinea versicolor: epidemiologic, clinical, and therapeutic aspects. J Am Acad Dermatol 25(2 Pt 1):300–305

    Article  CAS  PubMed  Google Scholar 

  3. Carrillo-Muñoz AJ, Rojas F, Tur-Tur C, de Los Ángeles Sosa M, Diez GO, Espada CM, Payá MJ, Giusiano G (2013) In vitro antifungal activity of topical and systemic antifungal drugs against Malassezia species. Mycoses 56(5):571–575

    Article  PubMed  Google Scholar 

  4. Crespo-Erchiga V, Florencio VD (2006) Malassezia yeasts and pityriasis versicolor. Curr Opin Infect Dis 19(2):139–147

    Article  PubMed  Google Scholar 

  5. Dorn M, Roehnert K (1977) Dimorphism of Pityrosporum orbiculare in a defined culture medium. J Invest Dermatol 69(2):244–248

    Article  CAS  PubMed  Google Scholar 

  6. Faergemann J, Aly R, Maibach HI (1983) Growth and filament production of Pityrosporum orbiculare and Pityrosporum ovale on human stratum corneum in vitro. Acta Derm Venereol 63(5):388–392

    CAS  PubMed  Google Scholar 

  7. Faergemann J, Ausma J, Borgers M (2006) In vitro activity of R126638 and ketoconazole against Malassezia species. Acta Derm Venereol 86(4):312–315

    Article  CAS  PubMed  Google Scholar 

  8. Faergemann J, Borgers M, Degreef H (2007) A new ketoconazole topical gel formulation in seborrhoeic dermatitis: an updated review of the mechanism. Expert Opin Pharmacother 8(9):1365–1371

    Article  CAS  PubMed  Google Scholar 

  9. Gaitanis G, Chasapi V, Velegraki A (2005) Novel application of the Masson-Fontana stain for demonstrating Malassezia species melanin-like pigment production in vitro and in clinical specimens. J Clin Microbiol 43(8):4147–4151

    Article  PubMed  PubMed Central  Google Scholar 

  10. Gaitanis G, Magiatis P, Hantschke M, Bassukas ID, Velegraki A (2012) The Malassezia genus in skin and systemic diseases. Clin Microbiol Rev 25(1):106–141

    Article  PubMed  PubMed Central  Google Scholar 

  11. Garau M, Pereiro M Jr, del Palacio A (2003) In vitro susceptibilities of Malassezia species to a new triazole, albaconazole (UR-9825), and other antifungal compounds. Antimicrob Agents Chemother 47(7):2342–2344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Guého E, Boekhout T, Ashbee HR, Guillot J, Van Belkum A, Faergemann J (1998) The role of Malassezia species in the ecology of human skin and as pathogens. Med Mycol 36(Suppl 1):220–229

    PubMed  Google Scholar 

  13. Guého E, Boekhout T, Begerow D (2010) Biodiversity, phylogeny and ultrastructure. In: Boekhout T, Guého E, Mayser P, Velegraki A (eds) Malassezia and the skin. Springer, Berlin, Heidelberg, pp 17–63

    Chapter  Google Scholar 

  14. Guillot J, Breugnot C, de Barros M, Chermette R (1998) Usefulness of modified Dixon’s medium for quantitative culture of Malassezia species from canine skin. J Vet Diagn Invest 10(4):384–386

    Article  CAS  PubMed  Google Scholar 

  15. Gupta AK, Kohli Y, Summerbell RC, Faergemann J (2001) Quantitative culture of Malassezia species from different body sites of individuals with or without dermatoses. Med Mycol 39(3):243–251

    Article  CAS  PubMed  Google Scholar 

  16. Gupta AK, Batra R, Bluhm R, Boekhout T, Dawson TL Jr (2004) Skin diseases associated with Malassezia species. J Am Acad Dermatol 51(5):785–798

    Article  PubMed  Google Scholar 

  17. Gupta AK, Cooper EA, Ryder JE, Nicol KA, Chow M, Chauhry MM (2004) Optimal management of fungal infections of the skin, hair, and nails. Am J Clin Dermatol 5(4):225–237

    Article  PubMed  Google Scholar 

  18. Intayot P, Youngchim S (2016) Comparison of biochemical characterizations with PCR amplification in identification of Malassezia species isolated from pityriasis versicolor and healthy volunteers. Chiang Mai Med J 55(Suppl 1):31–43

    Google Scholar 

  19. Jena DK, Sengupta S, Dwari BC, Ram MK (2005) Pityriasis versicolor in the pediatric age group. Indian J Dermatol Venereol Leprol 71(4):259–261

    Article  PubMed  Google Scholar 

  20. Kolecka A, Khayhan K, Arabatzis M, Velegraki A, Kostrzewa M, Andersson A, Scheynius A, Cafarchia C, Iatta R, Montagna MT, Youngchim S, Cabañes FJ, Hoopman P, Kraak B, Groenewald M, Boekhout T (2014) Efficient identification of Malassezia yeasts by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). Br J Dermatol 170(2):332–341

    Article  CAS  PubMed  Google Scholar 

  21. Krisanty RI, Bramono K, Made Wisnu I (2009) Identification of Malassezia species from pityriasis versicolor in Indonesia and its relationship with clinical characteristics. Mycoses 52(3):257–262

    Article  PubMed  Google Scholar 

  22. Lambers H, Piessens S, Bloem A, Pronk H, Finkel P (2006) Natural skin surface pH is on average below 5, which is beneficial for its resident flora. Int J Cosmet Sci 28(5):359–370

    Article  CAS  PubMed  Google Scholar 

  23. Midgley G (2000) The lipophilic yeasts state of the art and prospects. Med Mycol 38(Suppl. I):9–16

    Article  PubMed  Google Scholar 

  24. Montes LE (1970) Systemic abnormalities and the intracellular site of infection of the stratum corneum. JAMA 213(9):1469–1472

    Article  CAS  PubMed  Google Scholar 

  25. Pérez Blanco M, Urbina de Guanipa O, Fernández Zeppenfeldt G, Richard de Yegres N (1990) Effect of temperature and humidity on the frequency of pityriasis versicolor. Epidemiological study in the state of Falcón, Venezuela. Invest Clin 31(3):121–128

    PubMed  Google Scholar 

  26. Prohic A, Jovovic Sadikovic T, Krupalija-Fazlic M, Kuskunovic-Vlahovljak S (2016) Malassezia species in healthy skin and in dermatological conditions. Int J Dermatol 55(5):494–504

    Article  PubMed  Google Scholar 

  27. Rao GS, Kuruvilla M, Kumar P, Vinod V (2002) Clinico-epidermiological studies on tinea versicolor. Indian J Dermatol Venereol Leprol 68(4):208–209

    PubMed  Google Scholar 

  28. Rincón S, Cepero de García MC, Espinel-Ingroff A (2006) A modified Christensen’s urea and CLSI broth microdilution method for testing susceptibilities of six Malassezia species to voriconazole, itraconazole, and ketoconazole. J Clin Microbiol 44(9):3429–3431

    Article  PubMed  PubMed Central  Google Scholar 

  29. Rojas FD, Sosa Mde L, Fernández MS, Cattana ME, Córdoba SB, Giusiano GE (2014) Antifungal susceptibility of Malassezia furfur, Malassezia sympodialis, and Malassezia globosa to azole drugs and amphotericin B evaluated using a broth microdilution method. Med Mycol 52(6):641–646

    Article  CAS  PubMed  Google Scholar 

  30. Saadatzadeh MR, Ashbee HR, Holland KT, Ingham E (2001) Production of the mycelial phase of Malassezia in vitro. Med Mycol 39(6):487–493

    Article  CAS  PubMed  Google Scholar 

  31. Savin R (1996) Diagnosis and treatment of tinea versicolor. J Fam Pract 43(2):127–132

    CAS  PubMed  Google Scholar 

  32. Scheinfeld N (2008) Ketoconazole: a review of a workhorse antifungal molecule with a focus on new foam and gel formulations. Drugs Today (Barc) 44(5):369–380

    Article  CAS  Google Scholar 

  33. Schwartz RA (2004) Superficial fungal infections. Lancet 364(9440):1173–1182

    Article  PubMed  Google Scholar 

  34. Sharma A, Rabha D, Choraria S et al (2016) Clinicomycological profile of pityriasis versicolor in Assam. Indian J Pathol Microbiol 59(2):159–165

    Article  PubMed  Google Scholar 

  35. Sunenshine PJ, Schwartz RA, Janniger CK (1998) Tinea versicolor. Int J Dermatol 37(9):648–655

    Article  CAS  PubMed  Google Scholar 

  36. Tajima M, Sugita T, Harada S et al (2006) Detection of hyphae specific genes from Malassezia species using Megasort®. Nippon Ishinkin Gakkai Zasshi 47(Suppl 1):70

    Google Scholar 

  37. Velegraki A, Alexopoulos EC, Kritikou S, Gaitanis G (2004) Use of fatty acid RPMI 1640 media for testing susceptibilities of eight Malassezia species to the new triazole posaconazole and to six established antifungal agents by a modified NCCLS M27–A2 microdilution method and Etest. J Clin Microbiol 42(8):3589–3593

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Youngchim S, Nosanchuk JD, Pornsuwan S, Kajiwara S, Vanittanakom N (2013) The role of L-DOPA on melanization and mycelial production in Malassezia furfur. PLoS One 8(6):e63764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This study was financially supported by the Research Fund of the Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand. JDN is partly supported by NIH AI52733.

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Correspondence to Sirida Youngchim.

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Youngchim, S., Nosanchuk, J.D., Chongkae, S. et al. Ketoconazole inhibits Malassezia furfur morphogenesis in vitro under filamentation optimized conditions. Arch Dermatol Res 309, 47–53 (2017). https://doi.org/10.1007/s00403-016-1701-4

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  • DOI: https://doi.org/10.1007/s00403-016-1701-4

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