Inducible and constitutive activation of two polymorphic promoter alleles of the Candida albicans multidrug efflux pump MDR1

Antimicrobial Agents and Chemotherapy

Volumn 56, Issue 8, 2012, Pages 4490-4494

  Sasse, Christoph ^a   Schillig, Rebecca ^a   Reimund, Alexandra ^a   Merk, Julia ^a   Morschhäuser, Joachim ^a  

^a UNIVERSITY OF WÜRZBURG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ABC TRANSPORTER; ANTIFUNGAL AGENT; FLUCONAZOLE; GENOMIC DNA; MESSENGER RNA; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR CAP1; TRANSCRIPTION FACTOR MRR1; UNCLASSIFIED DRUG;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ALLELE; ARTICLE; CANDIDA ALBICANS; CANDIDIASIS; FUNGAL GENE; FUNGAL STRAIN; FUNGUS ISOLATION; GENE LOCUS; GENETIC TRANSCRIPTION; HUMAN; MDR1 GENE; MULTIDRUG RESISTANCE; NONHUMAN; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; PROMOTER REGION; TRANSCRIPTION REGULATION;

ALLELES; ANTIFUNGAL AGENTS; CANDIDA ALBICANS; CELL CYCLE PROTEINS; DRUG RESISTANCE, MULTIPLE, FUNGAL; FLUCONAZOLE; FUNGAL PROTEINS; LOSS OF HETEROZYGOSITY; P-GLYCOPROTEIN; PROMOTER REGIONS, GENETIC; TRANSCRIPTION FACTORS;

EID: 84864387155     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.00264-12     Document Type: Article

References (32)

1. Alarco AM, Raymond M. 1999. The bZip transcription factor Cap1p is involved in multidrug resistance and oxidative stress response in Candida albicans. J. Bacteriol. 181:700-708. (Pubitemid 29061549)
2. Bruzual I, Kumamoto CA. 2011. An MDR1 promoter allele with higher promoter activity is common in clinically isolated strains of Candida albicans. Mol. Genet. Genomics 286:347-357.
3. Coste A, et al. 2007. Genotypic evolution of azole resistance mechanisms in sequential Candida albicans isolates. Eukaryot. Cell 6:1889-1904. (Pubitemid 47585577)
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. Dunkel N, Blaß J, Rogers PD, Morschhäuser J. 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. (Pubitemid 352033303)
6. Franz R, et al. 1998. Multiple molecular mechanisms contribute to a stepwise development of fluconazole resistance in clinical Candida albicans strains. Antimicrob. Agents Chemother. 42:3065-3072. (Pubitemid 28553719)
7. Gupta V, et al. 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. (Pubitemid 28458486)
8. Harry JB, et al. 2005. Drug-induced regulation of the MDR1 promoter in Candida albicans. Antimicrob. Agents Chemother. 49:2785-2792. (Pubitemid 40917592)
9. Heilmann CJ, Schneider S, Barker KS, Rogers PD, Morschhäuser J. 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. Hiller D, Sanglard D, Morschhäuser J. 2006. Overexpression of the MDR1gene is sufficient to confer increased resistance to toxic compounds in Candida albicans. Antimicrob. Agents Chemother. 50:1365-1371.
11. Hiller D, Stahl S, Morschhäuser J. 2006. Multiple cis-acting sequences mediate upregulation of the MDR1 efflux pump in a fluconazole- resistant clinical Candida albicans isolate. Antimicrob. Agents Chemother. 50:2300-2308. (Pubitemid 43993166)
12. Jones T, et al. 2004. The diploid genome sequence of Candida albicans. Proc. Natl. Acad. Sci. U. S. A. 101:7329 -7334.
13. Karababa M, Coste AT, Rognon B, Bille J, Sanglard D. 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.
14. MacCallum DM, et al. 2010. Genetic dissection of azole resistance mechanisms in Candida albicans and their validation in a mouse model of disseminated infection. Antimicrob. Agents Chemother. 54:1476-1483.
15. Mogavero S, Tavanti A, Senesi S, Rogers PD, Morschhäuser J. 2011. Differential requirement of the transcription factor Mcm1 for activation of the Candida albicans multidrug efflux pump MDR1 by its regulators Mrr1 and Cap1. Antimicrob. Agents Chemother. 55:2061-2066.
16. Morschhäuser J. 2002. The genetic basis of fluconazole resistance development in Candida albicans. Biochim. Biophys. Acta 1587:240 -248.
17. Morschhäuser J. 2010. Regulation of multidrug resistance in pathogenic fungi. Fungal Genet. Biol. 47:94 -106.
18. Morschhäuser J, et al. 2007. The transcription factor Mrr1p controls expression of the MDR1 efflux pump and mediates multidrug resistance in Candida albicans. PLoS Pathog. 3:e164. doi:10.1371/journal. ppat.0030164.
19. Morschhäuser J, Michel S, Staib P. 1999. Sequential gene disruption in Candida albicans by FLP-mediated site-specific recombination. Mol. Microbiol. 32:547-556. (Pubitemid 29233899)
20. Riggle PJ, Kumamoto CA. 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. (Pubitemid 44956808)
21. Rognon B, Kozovska Z, Coste AT, Pardini G, Sanglard D. 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. (Pubitemid 46040691)
22. Rustchenko E. 2007. Chromosome instability in Candida albicans. FEMS Yeast Res. 7:2-11. (Pubitemid 46122025)
23. Sanglard D, Ischer F, Monod M, Bille J. 1996. Susceptibilities of Candida albicans multidrug transporter mutants to various antifungal agents and other metabolic inhibitors. Antimicrob. Agents Chemother. 40:2300-2305. (Pubitemid 26328036)
24. Sasse C, et al. 2011. The transcription factor Ndt80 does not contribute to Mrr1-, Tac1-, and Upc2-mediated fluconazole resistance in Candida albicans. PLoS One 6:e25623. doi:10.1371/journal.pone.0025623.
25. Schubert S, et al. 2011. Regulation of efflux pump expression and drug resistance by the transcription factors Mrr1, Upc2, and Cap1 in Candida albicans. Antimicrob. Agents Chemother. 55:2212-2223.
26. Schubert S, Popp C, Rogers PD, Morschhäuser J. 2011. Functional dissection of a Candida albicans zinc cluster transcription factor, the multidrug resistance regulator Mrr1. Eukaryot. Cell 10:1110-1121.
27. Schubert S, Rogers PD, Morschhäuser J. 2008. Gain-of-function mutations in the transcription factor MRR1 are responsible for overexpression of the MDR1 efflux pump in fluconazole-resistant Candida dubliniensis strains. Antimicrob. Agents Chemother. 52:4274-4280.
28. Selmecki A, Forche A, Berman J. 2010. Genomic plasticity of the human fungal pathogen Candida albicans. Eukaryot. Cell 9:991-1008.
29. White TC. 1997. The presence of an R467K amino acid substitution and loss of allelic variation correlate with an azole-resistant lanosterol 14αdemethylase in Candida albicans. Antimicrob. Agents Chemother. 41:1488-1494. (Pubitemid 27289673)
30. White TC, Marr KA, Bowden RA. 1998. Clinical, cellular, and molecular factors that contribute to antifungal drug resistance. Clin. Microbiol. Rev. 11:382- 402.
31. Wirsching S, Michel S, Köhler G, Morschhäuser J. 2000. Activation of the multiple drug resistance gene MDR1 in fluconazole-resistant, clinical Candida albicans strains is caused by mutations in a trans-regulatory factor. J. Bacteriol. 182:400-404. (Pubitemid 30030124)
32. Wirsching S, Michel S, Morschhäuser J. 2000. Targeted gene disruption in Candida albicans wild-type strains: the role of the MDR1 gene in fluconazole resistance of clinical Candida albicans isolates. Mol. Microbiol. 36:856-865. (Pubitemid 30326531)