1887

Abstract

We investigated the molecular basis of the tolerance of biofilms to antifungals using the miconazole as a model compound, and translated the resulting data to other antifungals. Sessile cells of Δ, lacking the transcription factor Efg1, showed increased susceptibility to miconazole, amphotericin B and caspofungin, whereas these sessile cells were equally resistant to fluconazole. The increased sensitivity to miconazole was, at least, partly due to an increased accumulation of miconazole in the cells as compared to wild-type or reintegrant Δ() sessile cells. By using a rat biofilm model, we further confirmed the role of Efg1 in the tolerance of biofilms to miconazole when grown .

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.041020-0
2012-06-01
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/jmm/61/6/813.html?itemId=/content/journal/jmm/10.1099/jmm.0.041020-0&mimeType=html&fmt=ahah

References

  1. Bink A., Govaert G., François I. E., Pellens K., Meerpoel L., Borgers M., Van Minnebruggen G., Vroome V., Cammue B. P., Thevissen K. 2010; A fungicidal piperazine-1-carboxamidine induces mitochondrial fission-dependent apoptosis in yeast. FEMS Yeast Res 10:812–818 [View Article][PubMed]
    [Google Scholar]
  2. Bink A., Vandenbosch D., Coenye T., Nelis H., Cammue B. P., Thevissen K. 2011; Superoxide dismutases are involved in Candida albicans biofilm persistence against miconazole. Antimicrob Agents Chemother 55:4033–4037 [View Article][PubMed]
    [Google Scholar]
  3. CLSI 2008; Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeast; Approved Standard, M27–A3. Wayne, PA: Clinical and Laboratory Standards Institute;
    [Google Scholar]
  4. Davis-Hanna A., Piispanen A. E., Stateva L. I., Hogan D. A. 2008; Farnesol and dodecanol effects on the Candida albicans Ras1-cAMP signalling pathway and the regulation of morphogenesis. Mol Microbiol 67:47–62 [View Article][PubMed]
    [Google Scholar]
  5. François I. E. J. A., Cammue B. P. A., Borgers M., Ausma J., Dispersyn G. D., Thevissen K. 2006; Azoles: mode of antifungal action and resistance development. Effect of miconazole on endogenous reactive oxygen species production in Candida albicans . Antiinfect Agents Med Chem 5:3–13 [CrossRef]
    [Google Scholar]
  6. François I. E., Bink A., Vandercappellen J., Ayscough K. R., Toulmay A., Schneiter R., van Gyseghem E., Van den Mooter G., Borgers M. other authors 2009; Membrane rafts are involved in intracellular miconazole accumulation in yeast cells. J Biol Chem 284:32680–32685 [View Article][PubMed]
    [Google Scholar]
  7. Gillum A. M., Tsay E. Y., Kirsch D. R. 1984; Isolation of the Candida albicans gene for orotidine-5′-phosphate decarboxylase by complementation of S. cerevisiae ura3 and E. coli pyrF mutations. Mol Gen Genet 198:179–182 [View Article][PubMed]
    [Google Scholar]
  8. Giusani A. D., Vinces M., Kumamoto C. A. 2002; Invasive filamentous growth of Candida albicans is promoted by Czf1p-dependent relief of Efg1p-mediated repression. Genetics 160:1749–1753[PubMed]
    [Google Scholar]
  9. Jain P., Akula I., Edlind T. 2003; Cyclic AMP signaling pathway modulates susceptibility of Candida species and Saccharomyces cerevisiae to antifungal azoles and other sterol biosynthesis inhibitors. Antimicrob Agents Chemother 47:3195–3201 [View Article][PubMed]
    [Google Scholar]
  10. Katragkou A., Chatzimoschou A., Simitsopoulou M., Dalakiouridou M., Diza-Mataftsi E., Tsantali C., Roilides E. 2008; Differential activities of newer antifungal agents against Candida albicans and Candida parapsilosis biofilms. Antimicrob Agents Chemother 52:357–360 [View Article][PubMed]
    [Google Scholar]
  11. Kelly S. L., Lamb D. C., Baldwin B. C., Corran A. J., Kelly D. E. 1997; Characterization of Saccharomyces cerevisiae CYP61, sterol Δ22-desaturase, and inhibition by azole antifungal agents. J Biol Chem 272:9986–9988 [View Article][PubMed]
    [Google Scholar]
  12. Kucharíková S., Tournu H., Holtappels M., Van Dijck P., Lagrou K. 2010; In vivo efficacy of anidulafungin against mature Candida albicans biofilms in a novel rat model of catheter-associated candidiasis. Antimicrob Agents Chemother 54:4474–4475 [View Article][PubMed]
    [Google Scholar]
  13. Kucharíková S., Tournu H., Lagrou K., Van Dijck P., Bujdáková H. 2011; Detailed comparison of Candida albicans and Candida glabrata biofilms under different conditions and their susceptibility to caspofungin and anidulafungin. J Med Microbiol 60:1261–1269 [View Article][PubMed]
    [Google Scholar]
  14. Kuhn D. M., George T., Chandra J., Mukherjee P. K., Ghannoum M. A. 2002a; Antifungal susceptibility of Candida biofilms: unique efficacy of amphotericin B lipid formulations and echinocandins. Antimicrob Agents Chemother 46:1773–1780 [View Article][PubMed]
    [Google Scholar]
  15. Kuhn D. M., Chandra J., Mukherjee P. K., Ghannoum M. A. 2002b; Comparison of biofilms formed by Candida albicans and Candida parapsilosis on bioprosthetic surfaces. Infect Immun 70:878–888 [View Article][PubMed]
    [Google Scholar]
  16. Kyle A. A., Dahl M. V. 2004; Topical therapy for fungal infections. Am J Clin Dermatol 5:443–451 [View Article][PubMed]
    [Google Scholar]
  17. Lachke S. A., Srikantha T., Soll D. R. 2003; The regulation of EFG1 in white-opaque switching in Candida albicans involves overlapping promoters. Mol Microbiol 48:523–536 [View Article][PubMed]
    [Google Scholar]
  18. Lamfon H., Porter S. R., McCullough M., Pratten J. 2004; Susceptibility of Candida albicans biofilms grown in a constant depth film fermentor to chlorhexidine, fluconazole and miconazole: a longitudinal study. J Antimicrob Chemother 53:383–385 [View Article][PubMed]
    [Google Scholar]
  19. Lo H. J., Köhler J. R., DiDomenico B., Loebenberg D., Cacciapuoti A., Fink G. R. 1997; Nonfilamentous C. albicans mutants are avirulent. Cell 90:939–949 [View Article][PubMed]
    [Google Scholar]
  20. Mateus C., Crow S. A. Jr, Ahearn D. G. 2004; Adherence of Candida albicans to silicone induces immediate enhanced tolerance to fluconazole. Antimicrob Agents Chemother 48:3358–3366 [View Article][PubMed]
    [Google Scholar]
  21. Mermel L. A., Farr B. M., Sherertz R. J., Raad I. I., O’Grady N., Harris J. S., Craven D. E. 2001; Guidelines for the management of intravascular catheter-related infections. Clin Infect Dis 32:1249–1272 [View Article][PubMed]
    [Google Scholar]
  22. Mukherjee P. K., Chandra J. 2004; Candida biofilm resistance. Drug Resist Updat 7:301–309 [View Article][PubMed]
    [Google Scholar]
  23. Nailis H., Coenye T., Van Nieuwerburgh F., Deforce D., Nelis H. J. 2006; Development and evaluation of different normalization strategies for gene expression studies in Candida albicans biofilms by real-time PCR. BMC Mol Biol 7:25 [View Article][PubMed]
    [Google Scholar]
  24. Peeters E., Nelis H. J., Coenye T. 2008; Comparison of multiple methods for quantification of microbial biofilms grown in microtiter plates. J Microbiol Methods 72:157–165 [View Article][PubMed]
    [Google Scholar]
  25. Perumal P., Mekala S., Chaffin W. L. 2007; Role for cell density in antifungal drug resistance in Candida albicans biofilms. Antimicrob Agents Chemother 51:2454–2463 [View Article][PubMed]
    [Google Scholar]
  26. Prasad T., Hameed S., Manoharlal R., Biswas S., Mukhopadhyay C. K., Goswami S. K., Prasad R. 2010; Morphogenic regulator EFG1 affects the drug susceptibilities of pathogenic Candida albicans . FEMS Yeast Res 10:587–596[PubMed]
    [Google Scholar]
  27. Ramage G., VandeWalle K., López-Ribot J. L., Wickes B. L. 2002; The filamentation pathway controlled by the Efg1 regulator protein is required for normal biofilm formation and development in Candida albicans . FEMS Microbiol Lett 214:95–100 [View Article][PubMed]
    [Google Scholar]
  28. Ramage G., Mowat E., Jones B., Williams C., Lopez-Ribot J. L. 2009; Our current understanding of fungal biofilms. Crit Rev Microbiol 35:340–355 [View Article][PubMed]
    [Google Scholar]
  29. Ricicová M., Kucharíková S., Tournu H., Hendrix J., Bujdáková H., Van Eldere J., Lagrou K., Van Dijck P. 2010; Candida albicans biofilm formation in a new in vivo rat model. Microbiology 156:909–919 [View Article][PubMed]
    [Google Scholar]
  30. Seneviratne C. J., Jin L., Samaranayake L. P. 2008; Biofilm lifestyle of Candida: a mini review. Oral Dis 14:582–590 [View Article][PubMed]
    [Google Scholar]
  31. Srikantha T., Tsai L. K., Daniels K., Soll D. R. 2000; EFG1 null mutants of Candida albicans switch but cannot express the complete phenotype of white-phase budding cells. J Bacteriol 182:1580–1591 [View Article][PubMed]
    [Google Scholar]
  32. Stoldt V. R., Sonneborn A., Leuker C. E., Ernst J. F. 1997; Efg1p, an essential regulator of morphogenesis of the human pathogen Candida albicans, is a member of a conserved class of bHLH proteins regulating morphogenetic processes in fungi. EMBO J 16:1982–1991 [View Article][PubMed]
    [Google Scholar]
  33. Tebarth B., Doedt T., Krishnamurthy S., Weide M., Monterola F., Dominguez A., Ernst J. F. 2003; Adaptation of the Efg1p morphogenetic pathway in Candida albicans by negative autoregulation and PKA-dependent repression of the EFG1 gene. J Mol Biol 329:949–962 [View Article][PubMed]
    [Google Scholar]
  34. Thevissen K., Marchand A., Chaltin P., Meert E. M., Cammue B. P. 2009; Antifungal carbazoles. Curr Med Chem 16:2205–2211 [View Article][PubMed]
    [Google Scholar]
  35. Vanden Bossche H., Marichal P., Willemsens G., Bellens D., Gorrens J., Roels I., Coene M. C., Le Jeune L., Janssen P. A. 1990; Saperconazole: a selective inhibitor of the cytochrome P-450-dependent ergosterol synthesis in Candida albicans,Aspergillus fumigatus and Trichophyton mentagrophytes . Mycoses 33:335–352[PubMed]
    [Google Scholar]
  36. Vandenbosch D., Braeckmans K., Nelis H. J., Coenye T. 2010; Fungicidal activity of miconazole against Candida spp. biofilms. J Antimicrob Chemother 65:694–700 [View Article][PubMed]
    [Google Scholar]
  37. Vinces M. D., Haas C., Kumamoto C. A. 2006; Expression of the Candida albicans morphogenesis regulator gene CZF1 and its regulation by Efg1p and Czf1p. Eukaryot Cell 5:825–835 [View Article][PubMed]
    [Google Scholar]
  38. Watamoto T., Samaranayake L. P., Jayatilake J. A., Egusa H., Yatani H., Seneviratne C. J. 2009; Effect of filamentation and mode of growth on antifungal susceptibility of Candida albicans . Int J Antimicrob Agents 34:333–339 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.041020-0
Loading
/content/journal/jmm/10.1099/jmm.0.041020-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error