Gain-of-function mutations in the transcription factor MRR1 are responsible for overexpression of the MDR1 efflux pump in fluconazole-resistant Candida dubliniensis strains

Antimicrobial Agents and Chemotherapy

Volumn 52, Issue 12, 2008, Pages 4274-4280

  Schubert, Sabrina ^a   Rogers, P David ^b,c   Morschhäuser, Joachim ^a  

^a UNIVERSITY OF WÜRZBURG   (Germany)

^b UNIVERSITY OF TENNESSEE HEALTH SCIENCE CENTER   (United States)

^c UNIVERSITY OF TENNESSEE COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FLUCONAZOLE;

ALLELE; ANTIFUNGAL RESISTANCE; ANTIFUNGAL SUSCEPTIBILITY; ARTICLE; CANDIDA DUBLINIENSIS; CONTROLLED STUDY; FUNGAL STRAIN; GENE DELETION; GENE MUTATION; GENE OVEREXPRESSION; GENE SEQUENCE; GENETIC TRANSCRIPTION; NONHUMAN; PRIORITY JOURNAL;

ANTIFUNGAL AGENTS; CANDIDA; DRUG RESISTANCE, FUNGAL; FLUCONAZOLE; GENE EXPRESSION REGULATION, FUNGAL; HUMANS; MICROBIAL SENSITIVITY TESTS; MUTATION; P-GLYCOPROTEIN; TRANSCRIPTION FACTORS; UP-REGULATION;

EID: 57049159416     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.00740-08     Document Type: Article

References (39)

1. Angiolella, L., A. R. Stringaro, F. De Bernardis, B. Posteraro, M. Bonito, L. Toccacieli, A. Torosantucci, M. Colone, M. Sanguinetti, A. Cassone, and A. T. Palamara. 2008. Increase of virulence and its phenotypic traits in drug-resistant strains of Candida albicans. Antimicrob. Agents Chemother. 52:927-936.
2. Coste, A., A. Selmecki, A. Forche, D. Diogo, M. E. Bougnoux, C. d'Enfert, J. Berman, and D. Sanglard. 2007. Genotypic evolution of azole resistance mechanisms in sequential Candida albicans isolates. Eukaryot. Cell 6:1889-1904.
3. Cowen, L. E., A. Nantel, M. S. Whiteway, D. Y. Thomas, D. C. Tessier, L. M. Kohn, and J. B. Anderson. 2002. Population genomics of drug resistance in Candida albicans. Proc. Natl. Acad. Sci. USA 99:9284-9289.
4. Cowen, L. E., D. Sanglard, D. Calabrese, C. Sirjusingh, J. B. Anderson, and L. M. Kohn. 2000. Evolution of drug resistance in experimental populations of Candida albicans. J. Bacteriol. 182:1515-1522.
5. Dunkel, N., J. Blaß, P. D. Rogers, and J. Morschhäuser. 2008. Mutations in the multidrug resistance regulator MRR1, followed by loss of heterozygosity, are the main cause of MDR1 overexpression in fluconazole-resistant Candida albicans strains. Mol. Microbiol. 69:827-840.
6. Fekete-Forgacs, K., L. Gyure, and B. Lenkey. 2000. Changes of virulence factors accompanying the phenomenon of induced fluconazole resistance in Candida albicans. Mycoses 43:273-279.
7. Gillum, A. M., E. Y. Tsay, and D. R. Kirsch. 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.
8. Gupta, V., A. Kohli, S. Krishnamurthy, N. Puri, S. A. Aalamgeer, S. Panwar, and R. Prasad. 1998. Identification of polymorphic mutant alleles of CaMDR1, a major facilitator of Candida albicans which confers multidrug resistance, and its in vitro transcriptional activation. Curr. Genet. 34:192-199.
9. Harry, J. B., B. G. Oliver, J. L. Song, P. M. Silver, J. T. Little, J. Choiniere, and T. C. White. 2005. Drug-induced regulation of the MDR1 promoter in Candida albicans. Antimicrob. Agents Chemother. 49:2785-2792.
10. Karababa, M., A. T. Coste, B. Rognon, J. Bille, and D. Sanglard. 2004. Comparison of gene expression profiles of Candida albicans azole-resistant clinical isolates and laboratory strains exposed to drugs inducing multidrug transporters. Antimicrob. Agents Chemother. 48:3064-3079.
11. Kirkpatrick, W. R., S. G. Revankar, R. K. McAtee, J. L. Lopez-Ribot, A. W. Fothergill, D. I. McCarthy, S. E. Sanche, R. A. Cantu, M. G. Rinaldi, and T. F. Patterson. 1998. Detection of Candida dubliniensis in oropharyngeal samples from human immunodeficiency virus-infected patients in North America by primary CHROMagar Candida screening and susceptibility testing of isolates. J. Clin. Microbiol. 36:3007-3012.
12. Köhler, G. A., T. C. White, and N. Agabian. 1997. Overexpression of a cloned IMP dehydrogenase gene of Candida albicans confers resistance to the specific inhibitor mycophenolic acid. J. Bacteriol. 179:2331-2338.
13. Martinez, M., J. L. Lopez-Ribot, W. R. Kirkpatrick, B. J. Coco, S. P. Bachmann, and T. F. Patterson. 2002. Replacement of Candida albicans with C. dubliniensis in human immunodeficiency virus-infected patients with oropharyngeal candidiasis treated with fluconazole. J. Clin. Microbiol. 40:3135-3139.
14. Millon, L., A. Manteaux, G. Reboux, C. Drobacheff, M. Monod, T. Barale, and Y. Michel-Briand. 1994. Fluconazole-resistant recurrent oral candidiasis in human immunodeficiency virus-positive patients: persistence of Candida albicans strains with the same genotype. J. Clin. Microbiol. 32:1115-1118.
15. Moran, G., C. Stokes, S. Thewes, B. Hube, D. C. Coleman, and D. Sullivan. 2004. Comparative genomics using Candida albicans DNA microarrays reveals absence and divergence of virulence-associated genes in Candida dubliniensis. Microbiology 150:3363-3382.
16. Moran, G., D. Sullivan, J. Morschhäuser, and D. Coleman. 2002. The Candida dubliniensis CdCDR1 gene is not essential for fluconazole resistance. Antimicrob. Agents Chemother. 46:2829-2841.
17. Moran, G. P., D. M. MacCallum, M. J. Spiering, D. C. Coleman, and D. J. Sullivan. 2007. Differential regulation of the transcriptional repressor NRG1 accounts for altered host-cell interactions in Candida albicans and Candida dubliniensis. Mol. Microbiol. 66:915-929.
18. Moran, G. P., D. Sanglard, S. M. Donnelly, D. B. Shanley, D. J. Sullivan, and D. C. Coleman. 1998. Identification and expression of multidrug transporters responsible for fluconazole resistance in Candida dubliniensis. Antimicrob. Agents Chemother. 42:1819-1830.
19. Moran, G. P., D. J. Sullivan, M. C. Henman, C. E. McCreary, B. J. Harrington, D. B. Shanley, and D. C. Coleman. 1997. Antifungal 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 Chemother. 41:617-623.
20. Morschhäuser, J. 2002. The genetic basis of fluconazole resistance development in Candida albicans. Biochim. Biophys. Acta 1587:240-248.
21. Morschhäuser, J., K. S. Barker, T. T. Liu, J. Blaß-Warmuth, R. Homayouni, and P. D. Rogers. 2007. The transcription factor Mrr1p controls expression of the MDR1 efflux pump and mediates multidrug resistance in Candida albicans. PLoS Pathog. 3:e164.
22. Perea, S., J. L. Lopez-Ribot, B. L. Wickes, W. R. Kirkpatrick, O. P. Dib, S. P. Bachmann, S. M. Keller, M. Martinez, and T. F. Patterson. 2002. Molecular mechanisms of fluconazole resistance in Candida dubliniensis isolates from human immunodeficiency virus-infected patients with oropharyngeal candidiasis. Antimicrob. Agents Chemother. 46:1695-1703.
23. Perea, S., and T. F. Patterson. 2002. Antifungal resistance in pathogenic fungi. Clin. Infect. Dis. 35:1073-1080.
24. Pinjon, E., C. J. Jackson, S. L. Kelly, D. Sanglard, G. Moran, D. C. Coleman, and D. J. Sullivan. 2005. Reduced azole susceptibility in genotype 3 Candida dubliniensis isolates associated with increased CdCDR1 and CdCDR2 expression. Antimicrob. Agents Chemother. 49:1312-1318.
25. Reuß, O., and J. Morschhäuser. 2006. A family of oligopeptide transporters is required for growth of Candida albicans on proteins. Mol. Microbiol. 60:795-812.
26. Reuß, O., Å. Vik, R. Kolter, and J. Morschhäuser. 2004. The SAT1 flipper, an optimized tool for gene disruption in Candida albicans. Gene 341:119-127.
27. Riggle, P. J., and C. A. Kumamoto. 2006. Transcriptional regulation of MDR1, encoding a drug efflux determinant, in fluconazole-resistant Candida albicans strains through an Mcm1p binding site. Eukaryot. Cell 5:1957-1968.
28. Rognon, B., Z. Kozovska, A. T. Coste, G. Pardini, and D. Sanglard. 2006. Identification of promoter elements responsible for the regulation of MDR1 from Candida albicans, a major facilitator transporter involved in azole resistance. Microbiology 152:3701-3722.
29. Ruhnke, M., A. Eigler, I. Tennagen, B. Geiseler, E. Engelmann, and M. Trautmann. 1994. Emergence of fluconazole-resistant strains of Candida albicans in patients with recurrent oropharyngeal candidosis and human immunodeficiency virus infection. J. Clin. Microbiol. 32:2092-2098.
30. Ruhnke, M., A. Schmidt-Westhausen, and J. Morschhäuser. 2000. Development of simultaneous resistance to fluconazole in Candida albicans and Candida dubliniensis in a patient with AIDS. J. Antimicrob. Chemother. 46:291-295.
31. Sanglard, D. 2002. Resistance of human fungal pathogens to antifungal drugs. Curr. Opin. Microbiol. 5:379-385.
32. Staib, P., G. P. Moran, D. J. Sullivan, D. C. Coleman, and J. Morschhäuser. 2001. Isogenic strain construction and gene targeting in Candida dubliniensis. J. Bacteriol. 183:2859-2865.
33. Staib, P., and J. Morschhäuser. 2005. Differential expression of the NRG1 repressor controls species-specific regulation of chlamydospore development in Candida albicans and Candida dubliniensis. Mol. Microbiol. 55:637-652.
34. Sullivan, D., and D. Coleman. 1998. Candida dubliniensis: characteristics and identification. J. Clin. Microbiol. 36:329-334.
35. Sullivan, D. J., G. P. Moran, and D. C. Coleman. 2005. Candida dubliniensis: ten years on. FEMS Microbiol. Lett. 253:9-17.
36. Sullivan, D. J., G. P. Moran, E. Pinjon, A. Al-Mosaid, C. Stokes, C. Vaughan, and D. C. Coleman. 2004. Comparison of the epidemiology, drug resistance mechanisms, and virulence of Candida dubliniensis and Candida albicans. FEMS Yeast Res. 4:369-376.
37. Sullivan, D. J., T. J. Westerneng, K. A. Haynes, D. E. Bennett, and D. C. Coleman. 1995. Candida dubliniensis sp. nov.: phenotypic and molecular characterization of a novel species associated with oral candidosis in HIV-infected individuals. Microbiology 141(Pt 7):1507-1521.
38. Wirsching, S., G. P. Moran, D. J. Sullivan, D. C. Coleman, and J. Morschhäuser. 2001. MDR1-mediated drug resistance in Candida dubliniensis. Antimicrob. Agents Chemother. 45:3416-3421.
39. Yan, L., J. D. Zhang, Y. B. Cao, P. H. Gao, and Y. Y. Jiang. 2007. Proteomic analysis reveals a metabolism shift in a laboratory fluconazole-resistant Candida albicans strain. J. Proteome Res. 6:2248-2256.