Regulation of multidrug resistance in pathogenic fungi

Fungal Genetics and Biology

Volumn 47, Issue 2, 2010, Pages 94-106

  Morschhäuser, Joachim ^a  

^a UNIVERSITY OF WÜRZBURG   (Germany)

Author keywords

Aspergillus; Candida; Cryptococcus; Efflux pumps; Gene expression; Genomic alterations; Transcription factors

Indexed keywords

ABC TRANSPORTER; AMOROLFINE; AMPHOTERICIN B; BENOMYL; CANDIDA ALBICANS AP 1 PROTEIN; CLOTRIMAZOLE; ECHINOCANDIN; FLUCONAZOLE; FLUCYTOSINE; ITRACONAZOLE; KETOCONAZOLE; METHOTREXATE; MULTIDRUG RESISTANCE PROTEIN 1; MULTIDRUG RESISTANCE REGULATOR PROTEIN; MYCOPHENOLIC ACID; TERBINAFINE; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR MCM1; TRANSCRIPTION FACTOR PDR1; TRANSCRIPTION FACTOR PDR3; TRANSCRIPTION FACTOR TAC1; UNCLASSIFIED DRUG; VORICONAZOLE;

ANTIFUNGAL RESISTANCE; ARTICLE; CANDIDA ALBICANS; CANDIDA GLABRATA; CHROMOSOME DUPLICATION; FUNGAL GENETICS; GENE AMPLIFICATION; GENE OVEREXPRESSION; GENETIC REGULATION; MOLECULAR MECHANICS; MULTIDRUG RESISTANCE; NONHUMAN; PRIORITY JOURNAL; REGULATORY MECHANISM; TRANSCRIPTION INITIATION; TRANSCRIPTION REGULATION;

ANTIFUNGAL AGENTS; ASPERGILLUS FUMIGATUS; CANDIDA ALBICANS; CRYPTOCOCCUS NEOFORMANS; DRUG RESISTANCE, MULTIPLE, FUNGAL; FUNGI; GENE EXPRESSION REGULATION, FUNGAL; HUMANS; TRANSCRIPTION FACTORS;

ASPERGILLUS; ASPERGILLUS FUMIGATUS; CANDIDA; CANDIDA ALBICANS; CANDIDA GLABRATA; FILOBASIDIELLA NEOFORMANS; FUNGI;

EID: 73749084037     PISSN: 10871845     EISSN: 10960937     Source Type: Journal    
DOI: 10.1016/j.fgb.2009.08.002     Document Type: Article

References (175)

1. Alarco A.M., Balan I., Talibi D., Mainville N., and Raymond M. AP1-mediated multidrug resistance in Saccharomyces cerevisiae requires FLR1 encoding a transporter of the major facilitator superfamily. Journal of Biological Chemistry 272 (1997) 19304-19313
2. Alarco A.M., and Raymond M. The bZip transcription factor Cap1p is involved in multidrug resistance and oxidative stress response in Candida albicans. Journal of Bacteriology 181 (1999) 700-708
3. Albertson G.D., Niimi M., Cannon R.D., and Jenkinson H.F. Multiple efflux mechanisms are involved in Candida albicans fluconazole resistance. Antimicrobial Agents and Chemotherapy 40 (1996) 2835-2841
4. Angiolella L., Stringaro A.R., De Bernardis F., Posteraro B., Bonito M., Toccacieli L., Torosantucci A., Colone M., Sanguinetti M., Cassone A., and Palamara A.T. Increase of virulence and its phenotypic traits in drug-resistant strains of Candida albicans. Antimicrobial Agents and Chemotherapy 52 (2008) 927-936
5. Balan I., Alarco A.M., and Raymond M. The Candida albicans CDR3 gene codes for an opaque-phase ABC transporter. Journal of Bacteriology 179 (1997) 7210-7218
6. Barchiesi F., Calabrese D., Sanglard D., Falconi Di Francesco L., Caselli F., Giannini D., Giacometti A., Gavaudan S., and Scalise G. Experimental induction of fluconazole resistance in Candida tropicalis ATCC 750. Antimicrobial Agents and Chemotherapy 44 (2000) 1578-1584
7. Bennett J.E., Izumikawa K., and Marr K.A. Mechanism of increased fluconazole resistance in Candida glabrata during prophylaxis. Antimicrobial Agents and Chemotherapy 48 (2004) 1773-1777
8. Ben-Yaacov R., Knoller S., Caldwell G.A., Becker J.M., and Koltin Y. Candida albicans gene encoding resistance to benomyl and methotrexate is a multidrug resistance gene. Antimicrobial Agents and Chemotherapy 38 (1994) 648-652
9. Borst A., Raimer M.T., Warnock D.W., Morrison C.J., and Arthington-Skaggs B.A. Rapid acquisition of stable azole resistance by Candida glabrata isolates obtained before the clinical introduction of fluconazole. Antimicrobial Agents and Chemotherapy 49 (2005) 783-787
10. Bouchara J.P., Zouhair R., Le Boudouil S., Renier G., Filmon R., Chabasse D., Hallet J.N., and Defontaine A. In-vivo selection of an azole-resistant petite mutant of Candida glabrata. Journal of Medical Microbiology 49 (2000) 977-984
11. Brun S., Berges T., Poupard P., Vauzelle-Moreau C., Renier G., Chabasse D., and Bouchara J.P. Mechanisms of azole resistance in petite mutants of Candida glabrata. Antimicrobial Agents and Chemotherapy 48 (2004) 1788-1796
12. Brun S., Dalle F., Saulnier P., Renier G., Bonnin A., Chabasse D., and Bouchara J.P. Biological consequences of petite mutations in Candida glabrata. Journal of Antimicrobial Chemotherapy 56 (2005) 307-314
13. Bruno V.M., and Mitchell A.P. Regulation of azole drug susceptibility by Candida albicans protein kinase CK2. Molecular Microbiology 56 (2005) 559-573
14. Calabrese D., Bille J., and Sanglard D. A novel multidrug efflux transporter gene of the major facilitator superfamily from Candida albicans (FLU1) conferring resistance to fluconazole. Microbiology 146 Pt 11 (2000) 2743-2754
15. Chen C.G., Yang Y.L., Shih H.I., Su C.L., and Lo H.J. CaNdt80 is involved in drug resistance in Candida albicans by regulating CDR1. Antimicrobial Agents and Chemotherapy 48 (2004) 4505-4512
16. Chen K.H., Miyazaki T., Tsai H.F., and Bennett J.E. The bZip transcription factor Cgap1p is involved in multidrug resistance and required for activation of multidrug transporter gene Cg FLR1 in Candida glabrata. Gene 386 (2007) 63-72
17. Chiranand W., McLeod I., Zhou H., Lynn J.J., Vega L.A., Myers H., Yates III J.R., Lorenz M.C., and Gustin M.C. CTA4 transcription factor mediates induction of nitrosative stress response in Candida albicans. Eukaryotic Cell 7 (2008) 268-278
18. Clark F.S., Parkinson T., Hitchcock C.A., and Gow N.A. Correlation between rhodamine 123 accumulation and azole sensitivity in Candida species: possible role for drug efflux in drug resistance. Antimicrobial Agents and Chemotherapy 40 (1996) 419-425
19. Coste A., Turner V., Ischer F., Morschhäuser J., Forche A., Selmecki A., Berman J., Bille J., and Sanglard D. 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 (2006) 2139-2156
20. Coste A., Selmecki A., Forche A., Diogo D., Bougnoux M.E., d'Enfert C., Berman J., and Sanglard D. Genotypic evolution of azole resistance mechanisms in sequential Candida albicans isolates. Eukaryotic Cell 6 (2007) 1889-1904
21. Coste A.T., Karababa M., Ischer F., Bille J., and Sanglard D. TAC1, transcriptional activator of CDR genes, is a new transcription factor involved in the regulation of Candida albicans ABC transporters CDR1 and CDR2. Eukaryotic Cell 3 (2004) 1639-1652
22. Coste A.T., Ramsdale M., Ischer F., and Sanglard D. Divergent functions of three Candida albicans zinc-cluster transcription factors (CTA4, ASG1 and CTF1) complementing pleiotropic drug resistance in Saccharomyces cerevisiae. Microbiology 154 (2008) 1491-1501
23. Coste A.T., Crittin J., Bauser C., Rohde B., and Sanglard D. Functional analysis of cis- and trans-acting elements of the Candida albicans CDR2 promoter with a novel promoter reporter system. Eukaryot Cell. 8 (2009) 1250-1267
24. Cowen L.E., Sanglard D., Calabrese D., Sirjusingh C., Anderson J.B., and Kohn L.M. Evolution of drug resistance in experimental populations of Candida albicans. Journal of Bacteriology 182 (2000) 1515-1522
25. da Silva Ferreira M.E., Capellaro J.L., dos Reis Marques E., Malavazi I., Perlin D., Park S., Anderson J.B., Colombo A.L., Arthington-Skaggs B.A., Goldman M.H., and Goldman G.H. In vitro evolution of itraconazole resistance in Aspergillus fumigatus involves multiple mechanisms of resistance. Antimicrobial Agents and Chemotherapy 48 (2004) 4405-4413
26. De Backer M.D., Ilyina T., Ma X.J., Vandoninck S., Luyten W.H., and Vanden Bossche H. Genomic profiling of the response of Candida albicans to itraconazole treatment using a DNA microarray. Antimicrobial Agents and Chemotherapy 45 (2001) 1660-1670
27. de Micheli M., Bille J., Schueller C., and Sanglard D. A common drug-responsive element mediates the upregulation of the Candida albicans ABC transporters CDR1 and CDR2, two genes involved in antifungal drug resistance. Molecular Microbiology 43 (2002) 1197-1214
28. Del Sorbo G., Schoonbeek H., and De Waard M.A. Fungal transporters involved in efflux of natural toxic compounds and fungicides. Fungal Genetics and Biology 30 (2000) 1-15
29. Dodgson A.R., Dodgson K.J., Pujol C., Pfaller M.A., and Soll D.R. Clade-specific flucytosine resistance is due to a single nucleotide change in the FUR1 gene of Candida albicans. Antimicrobial Agents and Chemotherapy 48 (2004) 2223-2227
30. Dogra S., Krishnamurthy S., Gupta V., Dixit B.L., Gupta C.M., Sanglard D., and Prasad R. Asymmetric distribution of phosphatidylethanolamine in C. albicans: possible mediation by CDR1, a multidrug transporter belonging to ATP binding cassette (ABC) superfamily. Yeast 15 (1999) 111-121
31. Du W., Coaker M., Sobel J.D., and Akins R.A. Shuttle vectors for Candida albicans: control of plasmid copy number and elevated expression of cloned genes. Current Genetics 45 (2004) 390-398
32. Dunkel N., Blass J., Rogers P.D., and Morschhäuser J. 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. Molecular Microbiology 69 (2008) 827-840
33. Dunkel N., Liu T.T., Barker K.S., Homayouni R., Morschhäuser J., and Rogers P.D. 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. Eukaryotic Cell 7 (2008) 1180-1190
34. Edlind M.P., Smith W.L., and Edlind T.D. Effects of cetylpyridinium chloride resistance and treatment on fluconazole activity versus Candida albicans. Antimicrobial Agents and Chemotherapy 49 (2005) 843-845
35. Ferrari S., Ischer F., Calabrese D., Posteraro B., Sanguinetti M., Fadda G., Rohde B., Bauser C., Bader O., and Sanglard D. Gain of function mutations in CgPDR1 of Candida glabrata not only mediate antifungal resistance but also enhance virulence. PLoS Pathogens 5 (2009) e1000268
36. Fling M.E., Kopf J., Tamarkin A., Gorman J.A., Smith H.A., and Koltin Y. Analysis of a Candida albicans gene that encodes a novel mechanism for resistance to benomyl and methotrexate. Molecular and General Genetics 227 (1991) 318-329
37. Florent M., Noel T., Ruprich-Robert G., Da Silva B., Fitton-Ouhabi V., Chastin C., Papon N., and Chapeland-Leclerc F. Nonsense and missense mutations in FCY2 and FCY1 genes are responsible for flucytosine resistance and flucytosine-fluconazole cross-resistance in clinical isolates of Candida lusitaniae. Antimicrobial Agents and Chemotherapy 53 (2009) 2982-2990
38. Franz R., Kelly S.L., Lamb D.C., Kelly D.E., Ruhnke M., and Morschhäuser J. Multiple molecular mechanisms contribute to a stepwise development of fluconazole resistance in clinical Candida albicans strains. Antimicrobial Agents and Chemotherapy 42 (1998) 3065-3072
39. Franz R., Michel S., and Morschhäuser J. A fourth gene from the Candida albicans CDR family of ABC transporters. Gene 220 (1998) 91-98
40. Franz R., Ruhnke M., and Morschhäuser J. Molecular aspects of fluconazole resistance development in Candida albicans. Mycoses 42 (1999) 453-458
41. Gaur M., Choudhury D., and Prasad R. Complete inventory of ABC proteins in human pathogenic yeast, Candida albicans. Journal of Molecular Microbiology and Biotechnology 9 (2005) 3-15
42. Gaur M., Puri N., Manoharlal R., Rai V., Mukhopadhayay G., Choudhury D., and Prasad R. MFS transportome of the human pathogenic yeast Candida albicans. BMC Genomics 9 (2008) 579
43. Gaur N.A., Puri N., Karnani N., Mukhopadhyay G., Goswami S.K., and Prasad R. Identification of a negative regulatory element which regulates basal transcription of a multidrug resistance gene CDR1 of Candida albicans. FEMS Yeast Research 4 (2004) 389-399
44. Gaur N.A., Manoharlal R., Saini P., Prasad T., Mukhopadhyay G., Hoefer M., Morschhauser J., and Prasad R. Expression of the CDR1 efflux pump in clinical Candida albicans isolates is controlled by a negative regulatory element. Biochemical and Biophysical Research Communications 332 (2005) 206-214
45. Gauthier C., Weber S., Alarco A.M., Alqawi O., Daoud R., Georges E., and Raymond M. Functional similarities and differences between Candida albicans Cdr1p and Cdr2p transporters. Antimicrobial Agents and Chemotherapy 47 (2003) 1543-1554
46. Ghannoum M.A., and Rice L.B. Antifungal agents: mode of action, mechanisms of resistance, and correlation of these mechanisms with bacterial resistance. Clinical Microbiology Reviews 12 (1999) 501-517
47. Goldman G.H., da Silva Ferreira M.E., dos Reis Marques E., Savoldi M., Perlin D., Park S., Godoy Martinez P.C., Goldman M.H., and Colombo A.L. Evaluation of fluconazole resistance mechanisms in Candida albicans clinical isolates from HIV-infected patients in Brazil. Diagnostic Microbiology and Infectious Disease 50 (2004) 25-32
48. Goldway M., Teff D., Schmidt R., Oppenheim A.B., and Koltin Y. Multidrug resistance in Candida albicans: disruption of the BENr gene. Antimicrobial Agents and Chemotherapy 39 (1995) 422-426
49. Gottesman M.M., and Pastan I. Biochemistry of multidrug resistance mediated by the multidrug transporter. Annual Review of Biochemistry 62 (1993) 385-427
50. Grkovic S., Brown M.H., and Skurray R.A. Regulation of bacterial drug export systems. Microbiology and Molecular Biology Reviews 66 (2002) 671-701
51. Gulshan K., and Moye-Rowley W.S. Multidrug resistance in fungi. Eukaryotic Cell 6 (2007) 1933-1942
52. Gupta V., Kohli A., Krishnamurthy S., Puri N., Aalamgeer S.A., Panwar S., and Prasad R. Identification of polymorphic mutant alleles of CaMDR1, a major facilitator of Candida albicans which confers multidrug resistance, and its in vitro transcriptional activation. Current Genetics 34 (1998) 192-199
53. Harry J.B., Oliver B.G., Song J.L., Silver P.M., Little J.T., Choiniere J., and White T.C. Drug-induced regulation of the MDR1 promoter in Candida albicans. Antimicrobial Agents and Chemotherapy 49 (2005) 2785-2792
54. Henry K.W., Cruz M.C., Katiyar S.K., and Edlind T.D. Antagonism of azole activity against Candida albicans following induction of multidrug resistance genes by selected antimicrobial agents. Antimicrobial Agents and Chemotherapy 43 (1999) 1968-1974
55. Hernaez M.L., Gil C., Pla J., and Nombela C. Induced expression of the Candida albicans multidrug resistance gene CDR1 in response to fluconazole and other antifungals. Yeast 14 (1998) 517-526
56. Hernandez S., Lopez-Ribot J.L., Najvar L.K., McCarthy D.I., Bocanegra R., and Graybill J.R. Caspofungin resistance in Candida albicans: correlating clinical outcome with laboratory susceptibility testing of three isogenic isolates serially obtained from a patient with progressive Candida esophagitis. Antimicrobial Agents and Chemotherapy 48 (2004) 1382-1383
57. Hiller D., Sanglard D., and Morschhäuser J. Overexpression of the MDR1 gene is sufficient to confer increased resistance to toxic compounds in Candida albicans. Antimicrobial Agents and Chemotherapy 50 (2006) 1365-1371
58. Hiller D., Stahl S., and Morschhäuser J. Multiple cis-acting sequences mediate upregulation of the MDR1 efflux pump in a fluconazole-resistant clinical Candida albicans isolate. Antimicrobial Agents and Chemotherapy 50 (2006) 2300-2308
59. Hitchcock C.A., Pye G.W., Troke P.F., Johnson E.M., and Warnock D.W. Fluconazole resistance in Candida glabrata. Antimicrobial Agents and Chemotherapy 37 (1993) 1962-1965
60. Hope W.W., Tabernero L., Denning D.W., and Anderson M.J. Molecular mechanisms of primary resistance to flucytosine in Candida albicans. Antimicrobial Agents and Chemotherapy 48 (2004) 4377-4386
61. Izumikawa K., Kakeya H., Tsai H.F., Grimberg B., and Bennett J.E. Function of Candida glabrata ABC transporter gene, PDH1. Yeast 20 (2003) 249-261
62. Jain P., Akula I., and Edlind T. Cyclic AMP signaling pathway modulates susceptibility of Candida species and Saccharomyces cerevisiae to antifungal azoles and other sterol biosynthesis inhibitors. Antimicrobial Agents and Chemotherapy 47 (2003) 3195-3201
63. Joseph-Horne T., Hollomon D., Loeffler R.S., and Kelly S.L. Cross-resistance to polyene and azole drugs in Cryptococcus neoformans. Antimicrobial Agents and Chemotherapy 39 (1995) 1526-1529
64. Karababa M., Coste A.T., Rognon B., Bille J., and Sanglard D. Comparison of gene expression profiles of Candida albicans azole-resistant clinical isolates and laboratory strains exposed to drugs inducing multidrug transporters. Antimicrobial Agents and Chemotherapy 48 (2004) 3064-3079
65. Karnani N., Gaur N.A., Jha S., Puri N., Krishnamurthy S., Goswami S.K., Mukhopadhyay G., and Prasad R. SRE1 and SRE2 are two specific steroid-responsive modules of Candida drug resistance gene 1 (CDR1) promoter. Yeast 21 (2004) 219-239
66. Katiyar S.K., and Edlind T.D. Identification and expression of multidrug resistance-related ABC transporter genes in Candida krusei. Medical Mycology 39 (2001) 109-116
67. Kaur R., Castano I., and Cormack B.P. Functional genomic analysis of fluconazole susceptibility in the pathogenic yeast Candida glabrata: roles of calcium signaling and mitochondria. Antimicrobial Agents and Chemotherapy 48 (2004) 1600-1613
68. 87 isomerase in a Cryptococcus neoformans strain from an AIDS patient. FEMS Microbiology Letters 122 (1994) 39-42
69. 5,6-desaturation. FEBS Letters 400 (1997) 80-82
70. Kelly S.L., Lamb D.C., and Kelly D.E. Y132H substitution in Candida albicans sterol 14α-demethylase confers fluconazole resistance by preventing binding to haem. FEMS Microbiology Letters 180 (1999) 171-175
71. Kelly S.L., Lamb D.C., Loeffler J., Einsele H., and Kelly D.E. The G464S amino acid substitution in Candida albicans sterol 14α-demethylase causes fluconazole resistance in the clinic through reduced affinity. Biochemical and Biophysical Research Communications 262 (1999) 174-179
72. Kohli A., Smriti, Mukhopadhyay K., Rattan A., and Prasad R. In vitro low-level resistance to azoles in Candida albicans is associated with changes in membrane lipid fluidity and asymmetry. Antimicrobial Agents and Chemotherapy 46 (2002) 1046-1052
73. Kolaczkowski M., and Goffeau A. Active efflux by multidrug transporters as one of the strategies to evade chemotherapy and novel practical implications of yeast pleiotropic drug resistance. Pharmacology & Therapeutics 76 (1997) 219-242
74. Krishnamurthy S., Gupta V., Prasad R., and Panwar S.L. Expression of CDR1, a multidrug resistance gene of Candida albicans: transcriptional activation by heat shock, drugs and human steroid hormones. FEMS Microbiology Letters 160 (1998) 191-197
75. Lamb D.C., Kelly D.E., Manning N.J., and Kelly S.L. Reduced intracellular accumulation of azole antifungal results in resistance in Candida albicans isolate NCPF 3363. FEMS Microbiology Letters 147 (1997) 189-193
76. Lamb D.C., Kelly D.E., White T.C., and Kelly S.L. The R467K amino acid substitution in Candida albicans sterol 14α-demethylase causes drug resistance through reduced affinity. Antimicrobial Agents and Chemotherapy 44 (2000) 63-67
77. Lamping E., Monk B.C., Niimi K., Holmes A.R., Tsao S., Tanabe K., Niimi M., Uehara Y., and Cannon R.D. Characterization of three classes of membrane proteins involved in fungal azole resistance by functional hyperexpression in Saccharomyces cerevisiae. Eukaryotic Cell 6 (2007) 1150-1165
78. Lamping E., Ranchod A., Nakamura K., Tyndall J.D., Niimi K., Holmes A.R., Niimi M., and Cannon R.D. Abc1p is a multidrug efflux transporter that tips the balance in favor of innate azole resistance in Candida krusei. Antimicrobial Agents and Chemotherapy 53 (2009) 354-369
79. Lavoie H., Sellam A., Askew C., Nantel A., and Whiteway M. A toolbox for epitope-tagging and genome-wide location analysis in Candida albicans. BMC Genomics 9 (2008) 578
80. Lee M.K., Williams L.E., Warnock D.W., and Arthington-Skaggs B.A. Drug resistance genes and trailing growth in Candida albicans isolates. Journal of Antimicrobial Chemotherapy 53 (2004) 217-224
81. Liu T.T., Lee R.E., Barker K.S., Wei L., Homayouni R., and Rogers P.D. Genome-wide expression profiling of the response to azole, polyene, echinocandin, and pyrimidine antifungal agents in Candida albicans. Antimicrobial Agents and Chemotherapy 49 (2005) 2226-2236
82. Liu T.T., Znaidi S., Barker K.S., Xu L., Homayouni R., Saidane S., Morschhäuser J., Nantel A., Raymond M., and Rogers P.D. Genome-wide expression and location analyses of the Candida albicans Tac1p regulon. Eukaryotic Cell 6 (2007) 2122-2138
83. Lopez-Ribot J.L., McAtee R.K., Lee L.N., Kirkpatrick W.R., White T.C., Sanglard D., and Patterson T.F. Distinct patterns of gene expression associated with development of fluconazole resistance in serial Candida albicans isolates from human immunodeficiency virus-infected patients with oropharyngeal candidiasis. Antimicrobial Agents and Chemotherapy 42 (1998) 2932-2937
84. Lopez-Ribot J.L., McAtee R.K., Perea S., Kirkpatrick W.R., Rinaldi M.G., and Patterson T.F. Multiple resistant phenotypes of Candida albicans coexist during episodes of oropharyngeal candidiasis in human immunodeficiency virus-infected patients. Antimicrobial Agents and Chemotherapy 43 (1999) 1621-1630
85. Lyons C.N., and White T.C. Transcriptional analyses of antifungal drug resistance in Candida albicans. Antimicrobial Agents and Chemotherapy 44 (2000) 2296-2303
86. MacPherson S., Larochelle M., and Turcotte B. A fungal family of transcriptional regulators: the zinc cluster proteins. Microbiology and Molecular Biology Reviews 70 (2006) 583-604
87. Manoharlal R., Gaur N.A., Panwar S.L., Morschhäuser J., and Prasad R. Transcriptional activation and increased mRNA stability contribute to overexpression of CDR1 in azole-resistant Candida albicans. Antimicrobial Agents and Chemotherapy 52 (2008) 1481-1492
88. Marichal P., Gorrens J., Coene M.C., Le Jeune L., and Vanden Bossche H. Origin of differences in susceptibility of Candida krusei to azole antifungal agents. Mycoses 38 (1995) 111-117
89. Marichal P., Vanden Bossche H., Odds F.C., Nobels G., Warnock D.W., Timmerman V., Van Broeckhoven C., Fay S., and Mose-Larsen P. Molecular biological characterization of an azole-resistant Candida glabrata isolate. Antimicrobial Agents and Chemotherapy 41 (1997) 2229-2237
90. Marr K.A., Lyons C.N., Rustad T.R., Bowden R.A., and White T.C. Rapid, transient fluconazole resistance in Candida albicans is associated with increased mRNA levels of CDR. Antimicrobial Agents and Chemotherapy 42 (1998) 2584-2589
91. Marr K.A., Lyons C.N., Ha K., Rustad T.R., and White T.C. Inducible azole resistance associated with a heterogeneous phenotype in Candida albicans. Antimicrobial Agents and Chemotherapy 45 (2001) 52-59
92. Martinez M., Lopez-Ribot J.L., Kirkpatrick W.R., Bachmann S.P., Perea S., Ruesga M.T., and Patterson T.F. Heterogeneous mechanisms of azole resistance in Candida albicans clinical isolates from an HIV-infected patient on continuous fluconazole therapy for oropharyngeal candidosis. Journal of Antimicrobial Chemotherapy 49 (2002) 515-524
93. Miyazaki H., Miyazaki Y., Geber A., Parkinson T., Hitchcock C., Falconer D.J., Ward D.J., Marsden K., and Bennett J.E. Fluconazole resistance associated with drug efflux and increased transcription of a drug transporter gene, PDH1, in Candida glabrata. Antimicrobial Agents and Chemotherapy 42 (1998) 1695-1701
94. Moran G., Sullivan D., Morschhäuser J., and Coleman D. The Candida dubliniensis CdCDR1 gene is not essential for fluconazole resistance. Antimicrobial Agents and Chemotherapy 46 (2002) 2829-2841
95. Moran G.P., Sanglard D., Donnelly S.M., Shanley D.B., Sullivan D.J., and Coleman D.C. Identification and expression of multidrug transporters responsible for fluconazole resistance in Candida dubliniensis. Antimicrobial Agents and Chemotherapy 42 (1998) 1819-1830
96. Morschhäuser J., Michel S., and Staib P. Sequential gene disruption in Candida albicans by FLP-mediated site-specific recombination. Molecular Microbiology 32 (1999) 547-556
97. Morschhäuser J. The genetic basis of fluconazole resistance development in Candida albicans. Biochimica et Biophysica Acta 1587 (2002) 240-248
98. Morschhäuser J., Barker K.S., Liu T.T., Blaß-Warmuth J., Homayouni R., and Rogers P.D. The transcription factor Mrr1p controls expression of the MDR1 efflux pump and mediates multidrug resistance in Candida albicans. PLoS Pathogens 3 (2007) e164
99. Moudgal V., Little T., Boikov D., and Vazquez J.A. Multiechinocandin and multiazole-resistant Candida parapsilosis isolates serially obtained during therapy for prosthetic valve endocarditis. Antimicrobial Agents and Chemotherapy 49 (2005) 767-769
100. Moye-Rowley W.S. Transcriptional control of multidrug resistance in the yeast Saccharomyces. Progress in Nucleic Acid Research and Molecular Biology 73 (2003) 251-279
101. Moye-Rowley W.S. Retrograde regulation of multidrug resistance in Saccharomyces cerevisiae. Gene 354 (2005) 15-21
102. Mukhopadhyay K., Prasad T., Saini P., Pucadyil T.J., Chattopadhyay A., and Prasad R. Membrane sphingolipid-ergosterol interactions are important determinants of multidrug resistance in Candida albicans. Antimicrobial Agents and Chemotherapy 48 (2004) 1778-1787
103. Nascimento A.M., Goldman G.H., Park S., Marras S.A., Delmas G., Oza U., Lolans K., Dudley M.N., Mann P.A., and Perlin D.S. Multiple resistance mechanisms among Aspergillus fumigatus mutants with high-level resistance to itraconazole. Antimicrobial Agents and Chemotherapy 47 (2003) 1719-1726
104. Niimi K., Maki K., Ikeda F., Holmes A.R., Lamping E., Niimi M., Monk B.C., and Cannon R.D. Overexpression of Candida albicans CDR1, CDR2, or MDR1 does not produce significant changes in echinocandin susceptibility. Antimicrobial Agents and Chemotherapy 50 (2006) 1148-1155
105. Niimi M., Nagai Y., Niimi K., Wada S., Cannon R.D., Uehara Y., and Monk B.C. Identification of two proteins induced by exposure of the pathogenic fungus Candida glabrata to fluconazole. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences 782 (2002) 245-252
106. Niimi M., Niimi K., Takano Y., Holmes A.R., Fischer F.J., Uehara Y., and Cannon R.D. Regulated overexpression of CDR1 in Candida albicans confers multidrug resistance. Journal of Antimicrobial Chemotherapy 54 (2004) 999-1006
107. Noel T., Francois F., Paumard P., Chastin C., Brethes D., and Villard J. Flucytosine-fluconazole cross-resistance in purine-cytosine permease-deficient Candida lusitaniae clinical isolates: indirect evidence of a fluconazole uptake transporter. Antimicrobial Agents and Chemotherapy 47 (2003) 1275-1284
108. Nolte F.S., Parkinson T., Falconer D.J., Dix S., Williams J., Gilmore C., Geller R., and Wingard J.R. Isolation and characterization of fluconazole- and amphotericin B-resistant Candida albicans from blood of two patients with leukemia. Antimicrobial Agents and Chemotherapy 41 (1997) 196-199
109. Orozco A.S., Higginbotham L.M., Hitchcock C.A., Parkinson T., Falconer D., Ibrahim A.S., Ghannoum M.A., and Filler S.G. Mechanism of fluconazole resistance in Candida krusei. Antimicrobial Agents and Chemotherapy 42 (1998) 2645-2649
110. Papon N., Noel T., Florent M., Gibot-Leclerc S., Jean D., Chastin C., Villard J., and Chapeland-Leclerc F. Molecular mechanism of flucytosine resistance in Candida lusitaniae: contribution of the FCY2, FCY1, and FUR1 genes to 5-fluorouracil and fluconazole cross-resistance. Antimicrobial Agents and Chemotherapy 51 (2007) 369-371
111. Parkinson T., Falconer D.J., and Hitchcock C.A. Fluconazole resistance due to energy-dependent drug efflux in Candida glabrata. Antimicrobial Agents and Chemotherapy 39 (1995) 1696-1699
112. Perea S., Lopez-Ribot J.L., Kirkpatrick W.R., McAtee R.K., Santillan R.A., Martinez M., Calabrese D., Sanglard D., and Patterson T.F. Prevalence of molecular mechanisms of resistance to azole antifungal agents in Candida albicans strains displaying high-level fluconazole resistance isolated from human immunodeficiency virus-infected patients. Antimicrobial Agents and Chemotherapy 45 (2001) 2676-2684
113. Perea S., Lopez-Ribot J.L., Wickes B.L., Kirkpatrick W.R., Dib O.P., Bachmann S.P., Keller S.M., Martinez M., and Patterson T.F. Molecular mechanisms of fluconazole resistance in Candida dubliniensis isolates from human immunodeficiency virus-infected patients with oropharyngeal candidiasis. Antimicrobial Agents and Chemotherapy 46 (2002) 1695-1703
114. Perlin D.S. Resistance to echinocandin-class antifungal drugs. Drug Resistance Updates 10 (2007) 121-130
115. Pinjon E., Moran G.P., Jackson C.J., Kelly S.L., Sanglard D., Coleman D.C., and Sullivan D.J. Molecular mechanisms of itraconazole resistance in Candida dubliniensis. Antimicrobial Agents and Chemotherapy 47 (2003) 2424-2437
116. Pinjon E., Jackson C.J., Kelly S.L., Sanglard D., Moran G., Coleman D.C., and Sullivan D.J. Reduced azole susceptibility in genotype 3 Candida dubliniensis isolates associated with increased CdCDR1 and CdCDR2 expression. Antimicrobial Agents and Chemotherapy 49 (2005) 1312-1318
117. Polakova S., Blume C., Zarate J.A., Mentel M., Jorck-Ramberg D., Stenderup J., and Piskur J. Formation of new chromosomes as a virulence mechanism in yeast Candida glabrata. Proceedings of the National Academy of Sciences USA 106 (2009) 2688-2693
118. Posteraro B., Sanguinetti M., Sanglard D., La Sorda M., Boccia S., Romano L., Morace G., and Fadda G. Identification and characterization of a Cryptococcus neoformans ATP binding cassette (ABC) transporter-encoding gene, CnAFR1, involved in the resistance to fluconazole. Molecular Microbiology 47 (2003) 357-371
119. Prasad R., De Wergifosse P., Goffeau A., and Balzi E. Molecular cloning and characterization of a novel gene of Candida albicans, CDR1, conferring multiple resistance to drugs and antifungals. Current Genetics 27 (1995) 320-329
120. Prasad T., Saini P., Gaur N.A., Vishwakarma R.A., Khan L.A., Haq Q.M., and Prasad R. Functional analysis of Ca IPT1, a sphingolipid biosynthetic gene involved in multidrug resistance and morphogenesis of Candida albicans. Antimicrobial Agents and Chemotherapy 49 (2005) 3442-3452
121. Puri N., Krishnamurthy S., Habib S., Hasnain S.E., Goswami S.K., and Prasad R. CDR1, a multidrug resistance gene from Candida albicans, contains multiple regulatory domains in its promoter and the distal AP-1 element mediates its induction by miconazole. FEMS Microbiology Letters 180 (1999) 213-219
122. Redding S.W., Kirkpatrick W.R., Saville S., Coco B.J., White W., Fothergill A., Rinaldi M., Eng T., Patterson T.F., and Lopez-Ribot J. Multiple patterns of resistance to fluconazole in Candida glabrata isolates from a patient with oropharyngeal candidiasis receiving head and neck radiation. Journal of Clinical Microbiology 41 (2003) 619-622
123. Riggle P.J., and Kumamoto C.A. Transcriptional regulation of MDR1, encoding a drug efflux determinant, in fluconazole-resistant Candida albicans strains through an Mcm1p binding site. Eukaryotic Cell 5 (2006) 1957-1968
124. Rognon B., Kozovska Z., Coste A.T., Pardini G., and Sanglard D. Identification of promoter elements responsible for the regulation of MDR1 from Candida albicans, a major facilitator transporter involved in azole resistance. Microbiology 152 (2006) 3701-3722
125. Rottmann M., Dieter S., Brunner H., and Rupp S. A screen in Saccharomyces cerevisiae identified CaMCM1, an essential gene in Candida albicans crucial for morphogenesis. Molecular Microbiology 47 (2003) 943-959
126. Rustad T.R., Stevens D.A., Pfaller M.A., and White T.C. Homozygosity at the Candida albicans MTL locus associated with azole resistance. Microbiology 148 (2002) 1061-1072
127. Ryley J.F., Wilson R.G., and Barrett-Bee K.J. Azole resistance in Candida albicans. Sabouraudia 22 (1984) 53-63
128. Saidane S., Weber S., De Deken X., St-Germain G., and Raymond M. PDR16-mediated azole resistance in Candida albicans. Molecular Microbiology 60 (2006) 1546-1562
129. Sanglard D., Kuchler K., Ischer F., Pagani J.L., Monod M., and Bille J. Mechanisms of resistance to azole antifungal agents in Candida albicans isolates from AIDS patients involve specific multidrug transporters. Antimicrobial Agents and Chemotherapy 39 (1995) 2378-2386
130. Sanglard D., Ischer F., Monod M., and Bille J. Susceptibilities of Candida albicans multidrug transporter mutants to various antifungal agents and other metabolic inhibitors. Antimicrobial Agents and Chemotherapy 40 (1996) 2300-2305
131. Sanglard D., Ischer F., Monod M., and Bille J. Cloning of Candida albicans genes conferring resistance to azole antifungal agents: characterization of CDR2, a new multidrug ABC transporter gene. Microbiology 143 Pt 2 (1997) 405-416
132. Sanglard D., Ischer F., Koymans L., and Bille J. Amino acid substitutions in the cytochrome P-450 lanosterol 14α-demethylase (CYP51A1) from azole-resistant Candida albicans clinical isolates contribute to resistance to azole antifungal agents. Antimicrobial Agents and Chemotherapy 42 (1998) 241-253
133. Sanglard D., Ischer F., Calabrese D., Majcherczyk P.A., and Bille J. The ATP binding cassette transporter gene Cg CDR1 from Candida glabrata is involved in the resistance of clinical isolates to azole antifungal agents. Antimicrobial Agents and Chemotherapy 43 (1999) 2753-2765
134. Sanglard D., Ischer F., and Bille J. Role of ATP-binding-cassette transporter genes in high-frequency acquisition of resistance to azole antifungals in Candida glabrata. Antimicrobial Agents and Chemotherapy 45 (2001) 1174-1183
135. Sanguinetti M., Posteraro B., Fiori B., Ranno S., Torelli R., and Fadda G. Mechanisms of azole resistance in clinical isolates of Candida glabrata collected during a hospital survey of antifungal resistance. Antimicrobial Agents and Chemotherapy 49 (2005) 668-679
136. Sanguinetti M., Posteraro B., La Sorda M., Torelli R., Fiori B., Santangelo R., Delogu G., and Fadda G. Role of AFR1, an ABC transporter-encoding gene, in the in vivo response to fluconazole and virulence of Cryptococcus neoformans. Infection and Immunity 74 (2006) 1352-1359
137. Schubert S., Rogers P.D., and Morschhäuser J. 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 52 (2008) 4274-4280
138. Schuetzer-Muehlbauer M., Willinger B., Krapf G., Enzinger S., Presterl E., and Kuchler K. The Candida albicans Cdr2p ATP-binding cassette (ABC) transporter confers resistance to caspofungin. Molecular Microbiology 48 (2003) 225-235
139. Sellam A., Tebbji F., and Nantel A. Role of Ndt80p in sterol metabolism regulation and azole resistance in Candida albicans. Eukaryotic Cell 8 (2009) 1174-1183
140. Selmecki A., Forche A., and Berman J. Aneuploidy and isochromosome formation in drug-resistant Candida albicans. Science 313 (2006) 367-370
141. Selmecki A., Gerami-Nejad M., Paulson C., Forche A., and Berman J. An isochromosome confers drug resistance in vivo by amplification of two genes, ERG11 and TAC1. Molecular Microbiology 68 (2008) 624-641
142. Silver P.M., Oliver B.G., and White T.C. Characterization of caspofungin susceptibilities by broth and agar in Candida albicans clinical isolates with characterized mechanisms of azole resistance. Medical Mycology 46 (2008) 231-239
143. Slaven J.W., Anderson M.J., Sanglard D., Dixon G.K., Bille J., Roberts I.S., and Denning D.W. Increased expression of a novel Aspergillus fumigatus ABC transporter gene, atrF, in the presence of itraconazole in an itraconazole resistant clinical isolate. Fungal Genetics and Biology 36 (2002) 199-206
144. Smith W.L., and Edlind T.D. Histone deacetylase inhibitors enhance Candida albicans sensitivity to azoles and related antifungals: correlation with reduction in CDR and ERG upregulation. Antimicrobial Agents and Chemotherapy 46 (2002) 3532-3539
145. Smriti, Krishnamurthy S., Dixit B.L., Gupta C.M., Milewski S., and Prasad R. ABC transporters Cdr1p, Cdr2p and Cdr3p of a human pathogen Candida albicans are general phospholipid translocators. Yeast 19 (2002) 303-318
146. Sternberg S. The emerging fungal threat. Science 266 (1994) 1632-1634
147. Talibi D., and Raymond M. Isolation of a putative Candida albicans transcriptional regulator involved in pleiotropic drug resistance by functional complementation of a pdr1 pdr3 mutation in Saccharomyces cerevisiae. Journal of Bacteriology 181 (1999) 231-240
148. Thakur J.K., Arthanari H., Yang F., Pan S.J., Fan X., Breger J., Frueh D.P., Gulshan K., Li D.K., Mylonakis E., Struhl K., Moye-Rowley W.S., Cormack B.P., Wagner G., and Naar A.M. A nuclear receptor-like pathway regulating multidrug resistance in fungi. Nature 452 (2008) 604-609
149. Thornewell S.J., Peery R.B., and Skatrud P.L. Cloning and characterization of CneMDR1: a Cryptococcus neoformans gene encoding a protein related to multidrug resistance proteins. Gene 201 (1997) 21-29
150. Tobin M.B., Peery R.B., and Skatrud P.L. Genes encoding multiple drug resistance-like proteins in Aspergillus fumigatus and Aspergillus flavus. Gene 200 (1997) 11-23
151. Torelli R., Posteraro B., Ferrari S., La Sorda M., Fadda G., Sanglard D., and Sanguinetti M. The ATP-binding cassette transporter-encoding gene CgSNQ2 is contributing to the CgPDR1-dependent azole resistance of Candida glabrata. Molecular Microbiology 68 (2008) 186-201
152. Tsai H.F., Krol A.A., Sarti K.E., and Bennett J.E. Candida glabrata PDR1, a transcriptional regulator of a pleiotropic drug resistance network, mediates azole resistance in clinical isolates and petite mutants. Antimicrobial Agents and Chemotherapy 50 (2006) 1384-1392
153. Tsao S., Rahkhoodaee F., and Raymond M. Relative contributions of the Candida albicans ABC transporters Cdr1p and Cdr2p to clinical azole resistance. Antimicrobial Agents and Chemotherapy 53 (2009) 1344-1352
154. Tuch B.B., Galgoczy D.J., Hernday A.D., Li H., and Johnson A.D. The evolution of combinatorial gene regulation in fungi. PLoS Biology 6 (2008) e38
155. van den Hazel H.B., Pichler H., do Valle Matta M.A., Leitner E., Goffeau A., and Daum G. PDR16 and PDR17, two homologous genes of Saccharomyces cerevisiae, affect lipid biosynthesis and resistance to multiple drugs. Journal of Biological Chemistry 274 (1999) 1934-1941
156. Vandeputte P., Tronchin G., Berges T., Hennequin C., Chabasse D., and Bouchara J.P. Reduced susceptibility to polyenes associated with a missense mutation in the ERG6 gene in a clinical isolate of Candida glabrata with pseudohyphal growth. Antimicrobial Agents and Chemotherapy 51 (2007) 982-990
157. Venkateswarlu K., Denning D.W., Manning N.J., and Kelly S.L. Resistance to fluconazole in Candida albicans from AIDS patients correlated with reduced intracellular accumulation of drug. FEMS Microbiology Letters 131 (1995) 337-341
158. Venkateswarlu K., Denning D.W., Manning N.J., and Kelly S.L. Reduced accumulation of drug in Candida krusei accounts for itraconazole resistance. Antimicrobial Agents and Chemotherapy 40 (1996) 2443-2446
159. Vermitsky J.P., and Edlind T.D. Azole resistance in Candida glabrata: coordinate upregulation of multidrug transporters and evidence for a Pdr1-like transcription factor. Antimicrobial Agents and Chemotherapy 48 (2004) 3773-3781
160. Vermitsky J.P., Earhart K.D., Smith W.L., Homayouni R., Edlind T.D., and Rogers P.D. Pdr1 regulates multidrug resistance in Candida glabrata: gene disruption and genome-wide expression studies. Molecular Microbiology 61 (2006) 704-722
161. Vogel M., Hartmann T., Koberle M., Treiber M., Autenrieth I.B., and Schumacher U.K. Rifampicin induces MDR1 expression in Candida albicans. Journal of Antimicrobial Chemotherapy 61 (2008) 541-547
162. Wada S., Niimi M., Niimi K., Holmes A.R., Monk B.C., Cannon R.D., and Uehara Y. Candida glabrata ATP-binding cassette transporters Cdr1p and Pdh1p expressed in a Saccharomyces cerevisiae strain deficient in membrane transporters show phosphorylation-dependent pumping properties. Journal of Biological Chemistry 277 (2002) 46809-46821
163. Wakiec R., Prasad R., Morschhäuser J., Barchiesi F., Borowski E., and Milewski S. Voriconazole and multidrug resistance in Candida albicans. Mycoses 50 (2007) 109-115
164. White T.C. 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. Antimicrobial Agents and Chemotherapy 41 (1997) 1482-1487
165. Willger S.D., Puttikamonkul S., Kim K.H., Burritt J.B., Grahl N., Metzler L.J., Barbuch R., Bard M., Lawrence C.B., and Cramer Jr. R.A. A sterol-regulatory element binding protein is required for cell polarity, hypoxia adaptation, azole drug resistance, and virulence in Aspergillus fumigatus. PLoS Pathogens 4 (2008) e1000200
166. Wirsching S., Michel S., Köhler G., and Morschhäuser J. Activation of the multiple drug resistance gene MDR1 in fluconazole-resistant, clinical Candida albicans strains is caused by mutations in a trans-regulatory factor. Journal of Bacteriology 182 (2000) 400-404
167. Wirsching S., Michel S., and Morschhäuser J. Targeted gene disruption in Candida albicans wild-type strains: the role of the MDR1 gene in fluconazole resistance of clinical Candida albicans isolates. Molecular Microbiology 36 (2000) 856-865
168. Wirsching S., Moran G.P., Sullivan D.J., Coleman D.C., and Morschhäuser J. MDR1-mediated drug resistance in Candida dubliniensis. Antimicrobial Agents and Chemotherapy 45 (2001) 3416-3421
169. Yan C., Lee L.H., and Davis L.I. Crm1p mediates regulated nuclear export of a yeast AP-1-like transcription factor. EMBO Journal 17 (1998) 7416-7429
170. Yan L., Zhang J., Li M., Cao Y., Xu Z., Gao P., Wang Y., and Jiang Y. DNA microarray analysis of fluconazole resistance in a laboratory Candida albicans strain. Acta Biochimica et Biophysica Sinica (Shanghai) 40 (2008) 1048-1060
171. Yang X., Talibi D., Weber S., Poisson G., and Raymond M. Functional isolation of the Candida albicans FCR3 gene encoding a bZip transcription factor homologous to Saccharomyces cerevisiae Yap3p. Yeast 18 (2001) 1217-1225
172. Young L.Y., Hull C.M., and Heitman J. Disruption of ergosterol biosynthesis confers resistance to amphotericin B in Candida lusitaniae. Antimicrobial Agents and Chemotherapy 47 (2003) 2717-2724
173. Zhang X., De Micheli M., Coleman S.T., Sanglard D., and Moye-Rowley W.S. Analysis of the oxidative stress regulation of the Candida albicans transcription factor, Cap1p. Molecular Microbiology 36 (2000) 618-629
174. Znaidi S., De Deken X., Weber S., Rigby T., Nantel A., and Raymond M. The zinc cluster transcription factor Tac1p regulates PDR16 expression in Candida albicans. Molecular Microbiology 66 (2007) 440-452
175. Znaidi S., Barker K.S., Weber S., Alarco A.M., Liu T.T., Boucher G., Rogers P.D., and Raymond M. Identification of the Candida albicans Cap1p regulon. Eukaryotic Cell 8 (2009) 806-820