An A643V amino acid substitution in Upc2p contributes to azole resistance in well-characterized clinical isolates of Candida albicans

Antimicrobial Agents and Chemotherapy

Volumn 55, Issue 2, 2011, Pages 940-942

  Hoot, Samantha J ^a   Smith, Adam R ^a   Brown, Ryan P ^a   White, Theodore C ^a,b  

^a SEATTLE BIOMEDICAL RESEARCH INSTITUTE   (United States)

^b UNIVERSITY OF WASHINGTON   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

A643V AMINO ACID; AMINO ACID DERIVATIVE; ERGOSTEROL; PYRROLE DERIVATIVE; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR UPC2P; UNCLASSIFIED DRUG;

AMINO ACID SUBSTITUTION; ANTIFUNGAL RESISTANCE; ANTIFUNGAL SUSCEPTIBILITY; ARTICLE; CANDIDA ALBICANS; ERG11 GENE; FUNGAL GENE; FUNGUS ISOLATION; GENE EXPRESSION; GENE FUNCTION; GENE MUTATION; GENE OVEREXPRESSION; GENETIC TRANSCRIPTION; NONHUMAN; PRIORITY JOURNAL;

AMINO ACID SUBSTITUTION; ANTIFUNGAL AGENTS; AZOLES; CANDIDA ALBICANS; DRUG RESISTANCE, FUNGAL; ERGOSTEROL; FLUCONAZOLE; FUNGAL PROTEINS; GENE EXPRESSION REGULATION, FUNGAL; HUMANS; MICROBIAL SENSITIVITY TESTS; SEQUENCE ANALYSIS, DNA; TRANS-ACTIVATORS;

EID: 78751695581     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.00995-10     Document Type: Article

References (23)

1. Abramova, N. E., et al. 2001. Regulatory mechanisms controlling expression of the DAN/TIR mannoprotein genes during anaerobic remodeling of the cell wall in Saccharomyces cerevisiae. Genetics 157:1169-1177.
2. Arthington-Skaggs, B. A., H. Jradi, T. Desai, and C. J. Morrison. 1999. Quantitation of ergosterol content: novel method for determination of fluconazole susceptibility of Candida albicans. J. Clin. Microbiol. 37:3332-3337.
3. Bourot, S., and F. Karst. 1995. Isolation and characterization of the Saccharomyces cerevisiae SUT1 gene involved in sterol uptake. Gene 165:97-102.
4. Coste, A., et al. 2006. A mutation in Tac1p, a transcription factor regulating CDR1 and CDR2, is coupled with loss of heterozygosity at chromosome 5 to mediate antifungal resistance in Candida albicans. Genetics 172:2139-2156.
5. Crowley, J. H., F. W. Leak, Jr., K. V. Shianna, S. Tove, and L. W. Parks. 1998. A mutation in a purported regulatory gene affects control of sterol uptake in Saccharomyces cerevisiae. J. Bacteriol. 180:4177-4183.
6. Davies, B. S., H. S. Wang, and J. Rine. 2005. Dual activators of the sterol biosynthetic pathway of Saccharomyces cerevisiae: similar activation/regulatory domains but different response mechanisms. Mol. Cell. Biol. 25:7375-7385.
7. Dunkel, N., J. Blass, P. D. Rogers, and J. Morschhauser. 2008. Mutations in the multi-drug 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.
8. Dunkel, N., T. T. Liu, K. S. Barker, R. Homayouni, J. Morschhauser, and P. D. Rogers. 2008. A gain-of-function mutation in the transcription factor Upc2p causes upregulation of ergosterol biosynthesis genes and increased fluconazole resistance in a clinical Candida albicans isolate. Eukaryot. Cell 7:1180-1190.
9. Heilmann, C. J., S. Schneider, K. S. Barker, P. D. Rogers, and J. Morschhauser. 2010. An A643T mutation in the transcription factor Upc2p causes constitutive ERG11 upregulation and increased fluconazole resistance in Candida albicans. Antimicrob. Agents Chemother. 54:353-359.
10. Hickman, M. J., and F. Winston. 2007. Heme levels switch the function of HapI of Saccharomyces cerevisiae between transcriptional activator and transcriptional repressor. Mol. Cell. Biol. 27:7414-7424.
11. Hongay, C., N. Jia, M. Bard, and F. Winston. 2002. Mot3 is a transcriptional repressor of ergosterol biosynthetic genes and is required for normal vacuolar function in Saccharomyces cerevisiae. EMBO J. 21:4114-4124. (Pubitemid 34857443)
12. Hoot, S. J., B. G. Oliver, and T. C. White. 2008. Candida albicans UPC2 is transcriptionally induced in response to antifungal drugs and anaerobicity through Upc2p-dependent and -independent mechanisms. Microbiology 154:2748-2756.
13. Marie, C., S. Leyde, and T. C. White. 2008. Cytoplasmic localization of sterol transcription factors Upc2p and Ecm22p in S. cerevisiae. Fungal Genet. Biol. 45:1430-1438.
14. Oliver, B. G., P. M. Silver, C. Marie, S. J. Hoot, S. E. Leyde, and T. C. White. 2008. Tetracycline alters drug susceptibility in Candida albicans and other pathogenic fungi. Microbiology 154:960-970.
15. Rogers, P. D., and K. S. Barker. 2003. Genome-wide expression profile analysis reveals coordinately regulated genes associated with stepwise acquisition of azole resistance in Candida albicans clinical isolates. Antimicrob. Agents Chemother. 47:1220-1227.
16. Silver, P. M., B. G. Oliver, and T. C. White. 2004. Role of Candida albicans transcription factor Upc2p in drug resistance and sterol metabolism. Eukaryot. Cell 3:1391-1397.
17. Vik, A., and J. Rine. 2001. Upc2p and Ecm22p, dual regulators of sterol biosynthesis in Saccharomyces cerevisiae. Mol. Cell. Biol. 21:6395-6405.
18. White, T. C. 1997. Increased mRNA levels of ERG16, CDR, and MDR1 correlate with increases in azole resistance in Candida albicans isolates from a patient infected with human immunodeficiency virus. Antimicrob. Agents Chemother. 41:1482-1487.
19. White, T. C., S. Holleman, F. Dy, L. F. Mirels, and D. A. Stevens. 2002. Resistance mechanisms in clinical isolates of Candida albicans. Antimicrob. Agents Chemother. 46:1704-1713.
20. White, T. C., and P. M. Silver. 2005. Regulation of sterol metabolism in Candida albicans by the UPC2 gene. Biochem. Soc. Trans. 33:1215-1218.
21. Wilcox, L. J., D. A. Balderes, B. Wharton, A. H. Tinkelenberg, G. Rao, and S. L. Sturley. 2002. Transcriptional profiling identifies two members of the ATP-binding cassette transporter superfamily required for sterol uptake in yeast. J. Biol. Chem. 277:32466-32472.
22. Wilson, R. B., D. Davis, and A. P. Mitchell. 1999. Rapid hypothesis testing with Candida albicans through gene disruption with short homology regions. J. Bacteriol. 181:1868-1874.
23. Znaidi, S., S. Weber, O. Z. Al-Abdin, P. Bomme, S. Saidane, S. Drouin, S. Lemieux, X. De Deken, F. Robert, and M. Raymond. 2008. Genomewide location analysis of Candida albicans Upc2p, a regulator of sterol metabolism and azole drug resistance. Eukaryot. Cell 7:836-847. (Pubitemid 351968827)