Skip to main content
SpringerLink
Log in

The Ins and Outs of Azole Antifungal Drug Resistance: Molecular Mechanisms of Transport

  • Reference work entry
  • First Online:
Book cover Handbook of Antimicrobial Resistance

Abstract

Azoles are a major class of antifungal drugs commonly used to treat pathogenic fungi. Azole antifungals are relatively inexpensive, share similar chemical structures, and are effective against most fungal species. Azoles target a crucial enzyme in the ergosterol biosynthesis pathway whose inhibition leads to reduced fungal growth. Azole treatment, combined with the host’s immune system, results in the elimination of the fungus from the host. Since azoles are fungistatic instead of fungicidal, their prolonged use and abuse often results in the development of resistance, which is a serious clinical problem in antifungal therapy. The main mechanisms by which fungi become resistant to azoles are increased efflux of the drug from the fungal cell, and modifications in the sterol biosynthesis pathway, especially in the azole target enzyme. In general, all known fungal pathogens share these two basic types of resistance mechanisms, although the specific efflux pumps or mutations in the sterol pathway may be unique for each fungus. This chapter summarizes the development of azole resistance in the major human fungal pathogen, Candida albicans, and compares these mechanisms to those in other fungal pathogens. Resistance to other non-azole antifungal drugs is also discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 449.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 699.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • 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

    CAS  PubMed  PubMed Central  Google Scholar 

  • Alcazar-Fuoli L, Mellado E, Garcia-Effron G, Buitrago MJ, Lopez JF, Grimalt JO, Cuenca-Estrella JM, Rodriguez-Tudela JL (2006) Aspergillus fumigatus C-5 sterol desaturases Erg3A and Erg3B: role in sterol biosynthesis and antifungal drug susceptibility. Antimicrob Agents Chemother 50:453–460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Anderson JB, Sirjusingh C, Parsons AB, Boone C, Wickens C, Cowen LE, Kohn LM (2003) Mode of selection and experimental evolution of antifungal drug resistance in Saccharomyces cerevisiae. Genetics 163:1287–1298

    CAS  PubMed  PubMed Central  Google Scholar 

  • Andreasen AA, Stier TJ (1953) Anaerobic nutrition of Saccharomyces cerevisiae. I Ergosterol requirement for growth in a defined medium. J Cell Physiol 41:23–36

    Article  CAS  Google Scholar 

  • Arendrup MC, Perkhofer S, Howard SJ, Garcia-Effron G, Vishukumar A, Perlin D, Lass-Florl C (2008) Establishing in vitro-in vivo correlations for Aspergillus fumigatus: the challenge of azoles versus echinocandins. Antimicrob Agents Chemother 52:3504–3511

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Arendrup MC, Garcia-Effron G, Buzina W, Mortensen KL, Reiter N, Lundin C, Jensen HE, Lass-Florl C, Perlin DS, Bruun B (2009) Breakthrough Aspergillus fumigatus and Candida albicans double infection during caspofungin treatment: laboratory characteristics and implication for susceptibility testing. Antimicrob Agents Chemother 53:1185–1193

    Article  CAS  PubMed  Google Scholar 

  • Bard M, Sturm AM, Pierson CA, Brown S, Rogers KM, Nabinger S, Eckstein J, Barbuch R, Lees ND, Howell SA, Hazen KC (2005) Sterol uptake in Candida glabrata: rescue of sterol auxotrophic strains. Diagn Microbiol Infect Dis 52:285–293

    Article  CAS  PubMed  Google Scholar 

  • Bennett RJ, Johnson AD (2003) Completion of a parasexual cycle in Candida albicans by induced chromosome loss in tetraploid strains. Embo J 22:2505–2515

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Billack B, Santoro M, Lau-Cam C (2009) Growth inhibitory action of ebselen on fluconazole-resistant Candida albicans: role of the plasma membrane H+ − ATPase. Microb Drug Resist 15:77–83

    Article  CAS  PubMed  Google Scholar 

  • Bouchara JP, Zouhair R, Le Boudouil S, Renier G, Filmon R, Chabasse D, Hallet JN, Defontaine A (2000) In-vivo selection of an azole-resistant petite mutant of Candida glabrata. J Med Microbiol 49:977–984

    Article  CAS  PubMed  Google Scholar 

  • Brun S, Dalle F, Saulnier P, Renier G, Bonnin A, Chabasse D, Bouchara JP (2005) Biological consequences of petite mutations in Candida glabrata. J Antimicrob Chemother 56:307–314

    Article  CAS  PubMed  Google Scholar 

  • Bruno VM, Mitchell AP (2005) Regulation of azole drug susceptibility by Candida albicans protein kinase CK2. Mol Microbiol 56:559–573

    Article  CAS  PubMed  Google Scholar 

  • Calabrese D, Bille J, Sanglard D (2000) A novel multidrug efflux transporter gene of the major facilitator superfamily from Candida albicans (FLU1) conferring resistance to fluconazole. Microbiology 146(Pt 11):2743–2754

    Article  CAS  PubMed  Google Scholar 

  • Campoli P, Perlin DS, Kristof AS, White TC, Filler SG, Sheppard DC (2013) Pharmacokinetics of posaconazole within epithelial cells and fungi: insights into potential mechanisms of action during treatment and prophylaxis. J Infect Dis 208:1717–1728

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Camps SM, Rijs AJ, Klaassen CH, Meis JF, O‘Gorman CM, Dyer PS, Melchers WJ, Verweij PE (2012a) Molecular epidemiology of Aspergillus fumigatus isolates harboring the TR34/L98H azole resistance mechanism. J Clin Microbiol 50:2674–2680

    Article  PubMed  PubMed Central  Google Scholar 

  • Camps SM, Dutilh BE, Arendrup MC, Rijs AJ, Snelders E, Huynen MA, Verweij PE, Melchers WJ (2012b) Discovery of a HapE mutation that causes azole resistance in Aspergillus fumigatus through whole genome sequencing and sexual crossing. PLoS One 7:e50034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chapeland-Leclerc F, Bouchoux J, Goumar A, Chastin C, Villard J, Noel T (2005) Inactivation of the FCY2 gene encoding purine-cytosine permease promotes cross-resistance to flucytosine and fluconazole in Candida lusitaniae. Antimicrob Agents Chemother 49:3101–3108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chau AS, Gurnani M, Hawkinson R, Laverdiere M, Cacciapuoti A, McNicholas PM (2005) Inactivation of sterol Delta5,6-desaturase attenuates virulence in Candida albicans. Antimicrob Agents Chemother 49:3646–3651

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen KH, Miyazaki T, Tsai HF, Bennett JE (2007) The bZip transcription factor Cgap1p is involved in multidrug resistance and required for activation of multidrug transporter gene CgFLR1 in Candida glabrata. Gene 386:63–72

    Article  CAS  PubMed  Google Scholar 

  • Costa C, Pires C, Cabrito TR, Renaudin A, Ohno M, Chibana H, Sa-Correia I, Teixeira MC (2013) Candida glabrata drug:H+ antiporter CgQdr2 confers imidazole drug resistance, being activated by transcription factor CgPdr1. Antimicrob Agents Chemother 57:3159–3167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Coste AT, Karababa M, Ischer F, Bille J, Sanglard D (2004) TAC1, transcriptional activator of CDR genes, is a new transcription factor involved in the regulation of Candida albicans ABC transporters CDR1 and CDR2. Eukaryot Cell 3:1639–1652

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Coste A, Turner V, Ischer F, Morschhauser J, Forche A, Selmecki A, Berman J, Bille J, Sanglard D (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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Coste A, Selmecki A, Forche A, Diogo D, Bougnoux ME, D‘Enfert C, Berman J, Sanglard D (2007) Genotypic evolution of azole resistance mechanisms in sequential Candida albicans isolates. Eukaryot Cell 6:1889–1904

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Coste AT, Crittin J, Bauser C, Rohde B, Sanglard D (2009) Functional analysis of cis- and trans-acting elements of the Candida albicans CDR2 promoter with a novel promoter reporter system. Eukaryot Cell 8:1250–1267

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cowen LE, Lindquist S (2005) Hsp90 potentiates the rapid evolution of new traits: drug resistance in diverse fungi. Science 309:2185–2189

    Article  CAS  PubMed  Google Scholar 

  • Crowley JH, Leak FW Jr, Shianna KV, Tove S, Parks LW (1998) A mutation in a purported regulatory gene affects control of sterol uptake in Saccharomyces cerevisiae. J Bacteriol 180:4177–4183

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cruz MC, Goldstein AL, Blankenship JR, Del Poeta M, Davis D, Cardenas ME, Perfect JR, McCusker JH, Heitman J (2002) Calcineurin is essential for survival during membrane stress in Candida albicans. Embo J 21:546–559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • da Silva Ferreira ME, Malavazi I, Savoldi M, Brakhage AA, Goldman MH, Kim HS, Nierman WC, Goldman GH (2006) Transcriptome analysis of Aspergillus fumigatus exposed to voriconazole. Curr Genet 50:32–44

    Article  PubMed  CAS  Google Scholar 

  • Davies BS, Wang HS, Rine J (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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • de Micheli M, Bille J, Schueller C, Sanglard D (2002) A common drug-responsive element mediates the upregulation of the Candida albicans ABC transporters CDR1 and CDR2, two genes involved in antifungal drug resistance. Mol Microbiol 43:1197–1214

    Article  PubMed  Google Scholar 

  • Denning DW, Venkateswarlu K, Oakley KL, Anderson MJ, Manning NJ, Stevens DA, Warnock DW, Kelly SL (1997) Itraconazole resistance in Aspergillus fumigatus. Antimicrob Agents Chemother 41:1364–1368

    CAS  PubMed  PubMed Central  Google Scholar 

  • Diaz-Guerra TM, Mellado E, Cuenca-Estrella M, Rodriguez-Tudela JL (2003) A point mutation in the 14alpha-sterol demethylase gene cyp51A contributes to itraconazole resistance in Aspergillus fumigatus. Antimicrob Agents Chemother 47:1120–1124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dick JD, Merz WG, Saral R (1980) Incidence of polyene-resistant yeasts recovered from clinical specimens. Antimicrob Agents Chemother 18:158–163

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Diwischek F, Morschhauser J, Holzgrabe U (2009) Cerulenin analogues as inhibitors of efflux pumps in drug-resistant Candida albicans. Arch Pharm (Weinheim) 342:150–164

    Article  CAS  Google Scholar 

  • Dodds Ashley ES, Lewis R, Lewis JS, Martin C, Andes D (2006) Pharmacology of systemic antifungal agents. Clin Infect Dis 43:S28–S39

    Article  CAS  Google Scholar 

  • Dunkel N, Liu TT, Barker KS, Homayouni R, Morschhauser J, Rogers PD (2008a) 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dunkel N, Blass J, Rogers PD, Morschhauser J (2008b) 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Esquivel BE, Smith AR, Zavrel M, White TC (2015) Azole drug import into the pathogenic fungus Aspergillus fumigatus. Antimicrob Agents and Chemother. 59-3390-3398

    Google Scholar 

  • Etzkorn FA, Chang ZY, Stolz LA, Walsh CT (1994) Cyclophilin residues that affect noncompetitive inhibition of the protein serine phosphatase activity of calcineurin by the cyclophilin.cyclosporin A complex. Biochemistry 33:2380–2388

    Article  CAS  PubMed  Google Scholar 

  • Ferrari S, Ischer F, Calabrese D, Posteraro B, Sanguinetti M, Fadda G, Rohde B, Bauser C, Bader O, Sanglard D (2009) Gain of function mutations in CgPDR1 of Candida glabrata not only mediate antifungal resistance but also enhance virulence. PLoS Pathog 5:e1000268

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fiori A, Van Dijck P (2012) Potent synergistic effect of doxycycline with fluconazole against Candida albicans is mediated by interference with iron homeostasis. Antimicrob Agents Chemother 56:3785–3796

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Flowers SA, Barker KS, Berkow EL, Toner G, Chadwick SG, Gygax SE, Morschhauser J, Rogers PD (2012) Gain-of-function mutations in UPC2 are a frequent cause of ERG11 upregulation in azole-resistant clinical isolates of Candida albicans. Eukaryot Cell 11:1289–1299

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fraczek MG, Bromley M, Buied A, Moore CB, Rajendran R, Rautemaa R, Ramage G, Denning DW, Bowyer P (2013) The cdr1B efflux transporter is associated with non-cyp51a-mediated itraconazole resistance in Aspergillus fumigatus. J Antimicrob Chemother 68:1486–1496

    Article  CAS  PubMed  Google Scholar 

  • Garcia-Effron G, Lee S, Park S, Cleary JD, Perlin DS (2009) Effect of Candida glabrata FKS1 and FKS2 mutations on echinocandin sensitivity and kinetics of 1,3-beta-d-glucan synthase: implication for the existing susceptibility breakpoint. Antimicrob Agents Chemother 53:3690–3699

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Geber A, Hitchcock CA, Swartz JE, Pullen FS, Marsden KE, Kwon-Chung KJ, Bennett JE (1995) Deletion of the Candida glabrata ERG3 and ERG11 genes: effect on cell viability, cell growth, sterol composition, and antifungal susceptibility. Antimicrob Agents Chemother 39:2708–2717

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guo Q, Sun S, Yu J, Li Y, Cao L (2008) Synergistic activity of azoles with amiodarone against clinically resistant Candida albicans tested by chequerboard and time-kill methods. J Med Microbiol 57:457–462

    Article  CAS  PubMed  Google Scholar 

  • Hameed S, Dhamgaye S, Singh A, Goswami SK, Prasad R (2011) Calcineurin signaling and membrane lipid homeostasis regulates iron mediated multidrug resistance mechanisms in Candida albicans. PLoS One 6:e18684

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hawser SP, Douglas LJ (1995) Resistance of Candida albicans biofilms to antifungal agents in vitro. Antimicrob Agents Chemother 39:2128–2131

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heilmann CJ, Schneider S, Barker KS, Rogers PD, Morschhauser 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

    Article  CAS  PubMed  Google Scholar 

  • Henry KW, Nickels JT, Edlind TD (2000) Upregulation of ERG genes in Candida species by azoles and other sterol biosynthesis inhibitors. Antimicrob Agents Chemother 44:2693–2700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hiraga K, Yamamoto S, Fukuda H, Hamanaka N, Oda K (2005) Enniatin has a new function as an inhibitor of Pdr5p, one of the ABC transporters in Saccharomyces cerevisiae. Biochem Biophys Res Commun 328:1119–1125

    Article  CAS  PubMed  Google Scholar 

  • Hitchcock CA (1991) Cytochrome P-450-dependent 14 alpha-sterol demethylase of Candida albicans and its interaction with azole antifungals. Biochem Soc Trans 19:782–787

    Article  CAS  PubMed  Google Scholar 

  • Holmes AR, Keniya MV, Ivnitski-Steele I, Monk BC, Lamping E, Sklar LA, Cannon RD (2012) The monoamine oxidase A inhibitor clorgyline is a broad-spectrum inhibitor of fungal ABC and MFS transporter efflux pump activities which reverses the azole resistance of Candida albicans and Candida glabrata clinical isolates. Antimicrob Agents Chemother 56:1508–1515

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoot SJ, Smith AR, Brown RP, White TC (2011) An A643V amino acid substitution in Upc2p contributes to azole resistance in well-characterized clinical isolates of Candida albicans. Antimicrob Agents Chemother 55:940–942

    Article  CAS  PubMed  Google Scholar 

  • Hope WW, Tabernero L, Denning DW, Anderson MJ (2004) Molecular mechanisms of primary resistance to flucytosine in Candida albicans. Antimicrob Agents Chemother 48:4377–4386

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Howard SJ, Arendrup MC (2011) Acquired antifungal drug resistance in Aspergillus fumigatus: epidemiology and detection. Med Mycol 49(Suppl 1):S90–S95

    Article  CAS  PubMed  Google Scholar 

  • Howard SJ, Webster I, Moore CB, Gardiner RE, Park S, Perlin DS, Denning DW (2006) Multi-azole resistance in Aspergillus fumigatus. Int J Antimicrob Agents 28:450–453

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jensen-Pergakes KL, Kennedy MA, Lees ND, Barbuch R, Koegel C, Bard M (1998) Sequencing, disruption, and characterization of the Candida albicans sterol methyltransferase (ERG6) gene: drug susceptibility studies in erg6 mutants. Antimicrob Agents Chemother 42:1160–1167

    CAS  PubMed  PubMed Central  Google Scholar 

  • Joseph-Horne T, Hollomon D, Loeffler RS, Kelly SL (1995) Cross-resistance to polyene and azole drugs in Cryptococcus neoformans. Antimicrob Agents Chemother 39:1526–1529

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kafadar KA, Cyert MS (2004) Integration of stress responses: modulation of calcineurin signaling in Saccharomyces cerevisiae by protein kinase A. Eukaryot Cell 3:1147–1153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kelly SL, Lamb DC, Corran AJ, Baldwin BC, Kelly DE (1995) Mode of action and resistance to azole antifungals associated with the formation of 14 alpha-methylergosta-8,24(28)-dien-3 beta,6 alpha-diol. Biochem Biophys Res Commun 207:910–915

    Article  CAS  PubMed  Google Scholar 

  • Kelly SL, Lamb DC, Kelly DE, Manning NJ, Loeffler J, Hebart H, Schumacher U, Einsele H (1997) Resistance to fluconazole and cross-resistance to amphotericin B in Candida albicans from AIDS patients caused by defective sterol delta5,6-desaturation. FEBS Lett 400:80–82

    Article  CAS  PubMed  Google Scholar 

  • Kissinger CR, Parge HE, Knighton DR, Lewis CT, Pelletier LA, Tempczyk A, Kalish VJ, Tucker KD, Showalter RE, Moomaw EW et al (1995) Crystal structures of human calcineurin and the human FKBP12-FK506-calcineurin complex. Nature 378:641–644

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi T, Kakeya H, Miyazaki T, Izumikawa K, Yanagihara K, Ohno H, Yamamoto Y, Tashiro T, Kohno S (2011) Synergistic antifungal effect of lactoferrin with azole antifungals against Candida albicans and a proposal for a new treatment method for invasive candidiasis. Jpn J Infect Dis 64:292–296

    CAS  PubMed  Google Scholar 

  • Lamb DC, Corran A, Baldwin BC, Kwon-Chung J, Kelly SL (1995) Resistant P45051A1 activity in azole antifungal tolerant Cryptococcus neoformans from AIDS patients. FEBS Lett 368:326–330

    Article  CAS  PubMed  Google Scholar 

  • Lamoth F, Juvvadi PR, Gehrke C, Steinbach WJ (2013) In vitro activity of calcineurin and heat shock protein 90 Inhibitors against Aspergillus fumigatus azole- and echinocandin-resistant strains. Antimicrob Agents Chemother 57:1035–1039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lamping E, Monk BC, Niimi K, Holmes AR, Tsao S, Tanabe K, Niimi M, Uehara Y, Cannon RD (2007) Characterization of three classes of membrane proteins involved in fungal azole resistance by functional hyperexpression in Saccharomyces cerevisiae. Eukaryot Cell 6:1150–1165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lamping E, Ranchod A, Nakamura K, Tyndall JD, Niimi K, Holmes AR, Niimi M, Cannon RD (2009) Abc1p is a multidrug efflux transporter that tips the balance in favor of innate azole resistance in Candida krusei. Antimicrob Agents Chemother 53:354–369

    Article  CAS  PubMed  Google Scholar 

  • Lee KK, Maccallum DM, Jacobsen MD, Walker LA, Odds FC, Gow NA, Munro CA (2012) Elevated cell wall chitin in Candida albicans confers echinocandin resistance in vivo. Antimicrob Agents Chemother 56:208–217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lewis TA, Taylor FR, Parks LW (1985) Involvement of heme biosynthesis in control of sterol uptake by Saccharomyces cerevisiae. J Bacteriol 163:199–207

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lewis TL, Keesler GA, Fenner GP, Parks LW (1988) Pleiotropic mutations in Saccharomyces cerevisiae affecting sterol uptake and metabolism. Yeast 4:93–106

    Article  CAS  PubMed  Google Scholar 

  • Lewis RE, Kontoyiannis DP, Darouiche RO, Raad II, Prince RA (2002) Antifungal activity of amphotericin B, fluconazole, and voriconazole in an in vitro model of Candida catheter-related bloodstream infection. Antimicrob Agents Chemother 46:3499–3505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lopez-Ribot JL (2005) Candida albicans biofilms: more than filamentation. Curr Biol 15:R453–R455

    Article  CAS  PubMed  Google Scholar 

  • MacPherson S, Akache B, Weber S, De Deken X, Raymond M, Turcotte B (2005) Candida albicans zinc cluster protein Upc2p confers resistance to antifungal drugs and is an activator of ergosterol biosynthetic genes. Antimicrob Agents Chemother 49:1745–1752

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Manavathu EK, Vazquez JA, Chandrasekar PH (1999) Reduced susceptibility in laboratory-selected mutants of Aspergillus fumigatus to itraconazole due to decreased intracellular accumulation of the antifungal agent. Int J Antimicrob Agents 12:213–219

    Article  CAS  PubMed  Google Scholar 

  • Manoharlal R, Gaur NA, Panwar SL, Morschhauser J, Prasad R (2008) Transcriptional activation and increased mRNA stability contribute to overexpression of CDR1 in azole-resistant Candida albicans. Antimicrob Agents Chemother 52:1481–1492

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mansfield BE, Oltean HN, Oliver BG, Hoot SJ, Leyde SE, Hedstrom L, White TC (2010) Azole drugs are imported by facilitated diffusion in Candida albicans and other pathogenic fungi. PLoS Pathog 6:e1001126

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Marichal P, Vanden Bossche H, Odds FC, Nobels G, Warnock DW, Timmerman V, Van Broeckhoven C, Fay S, Mose-Larsen P (1997) Molecular biological characterization of an azole-resistant Candida glabrata isolate. Antimicrob Agents Chemother 41:2229–2237

    CAS  PubMed  PubMed Central  Google Scholar 

  • Marichal P, Koymans L, Willemsens S, Bellens D, Verhasselt P, Luyten W, Borgers M, Ramaekers FC, Odds FC, Bossche HV (1999) Contribution of mutations in the cytochrome P450 14alpha-demethylase (Erg11p, Cyp51p) to azole resistance in Candida albicans. Microbiology 145(Pt 10):2701–2713

    Article  CAS  PubMed  Google Scholar 

  • Mayer FL, Wilson D, Hube B (2013) Candida albicans pathogenicity mechanisms. Virulence 4:119–128

    Article  PubMed  PubMed Central  Google Scholar 

  • Mellado E, Diaz-Guerra TM, Cuenca-Estrella M, Rodriguez-Tudela JL (2001) Identification of two different 14-alpha sterol demethylase-related genes (cyp51A and cyp51B) in Aspergillus fumigatus and other Aspergillus species. J Clin Microbiol 39:2431–2438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mellado E, Garcia-Effron G, Alcazar-Fuoli L, Cuenca-Estrella M, Rodriguez-Tudela JL (2004) Substitutions at methionine 220 in the 14alpha-sterol demethylase (Cyp51A) of Aspergillus fumigatus are responsible for resistance in vitro to azole antifungal drugs. Antimicrob Agents Chemother 48:2747–2750

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mellado E, Garcia-Effron G, Alcazar-Fuoli L, Melchers WJ, Verweij PE, Cuenca-Estrella M, Rodriguez-Tudela JL (2007) A new Aspergillus fumigatus resistance mechanism conferring in vitro cross-resistance to azole antifungals involves a combination of cyp51A alterations. Antimicrob Agents Chemother 51:1897–1904

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miyazaki T, Miyazaki Y, Izumikawa K, Kakeya H, Miyakoshi S, Bennett JE, Kohno S (2006) Fluconazole treatment is effective against a Candida albicans erg3/erg3 mutant in vivo despite in vitro resistance. Antimicrob Agents Chemother 50:580–586

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morschhauser J (2002) The genetic basis of fluconazole resistance development in Candida albicans. Biochim Biophys Acta 1587:240–248

    Article  CAS  PubMed  Google Scholar 

  • Morschhauser J, Barker KS, Liu TT, Bla BWJ, Homayouni R, Rogers PD (2007) The transcription factor Mrr1p controls expression of the MDR1 efflux pump and mediates multidrug resistance in Candida albicans. PLoS Pathog 3:e164

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Nagi M, Tanabe K, Ueno K, Nakayama H, Aoyama T, Chibana H, Yamagoe S, Umeyama T, Oura T, Ohno H, Kajiwara S, Miyazaki Y (2013) The Candida glabrata sterol scavenging mechanism, mediated by the ATP-binding cassette transporter Aus1p, is regulated by iron limitation. Mol Microbiol 88:371–381

    Article  CAS  PubMed  Google Scholar 

  • Nakayama H, Tanabe K, Bard M, Hodgson W, Wu S, Takemori D, Aoyama T, Kumaraswami NS, Metzler L, Takano Y, Chibana H, Niimi M (2007) The Candida glabrata putative sterol transporter gene CgAUS1 protects cells against azoles in the presence of serum. J Antimicrob Chemother 60:1264–1272

    Article  CAS  PubMed  Google Scholar 

  • Nett J, Lincoln L, Marchillo K, Massey R, Holoyda K, Hoff B, VanHandel M, Andes D (2007) Putative role of beta-1,3 glucans in Candida albicans biofilm resistance. Antimicrob Agents Chemother 51:510–520

    Article  CAS  PubMed  Google Scholar 

  • Nett JE, Sanchez H, Cain MT, Andes DR (2010) Genetic basis of Candida biofilm resistance due to drug-sequestering matrix glucan. J Infect Dis 202:171–175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nierman WC, Pain A, Anderson MJ, Wortman JR, Kim HS, Arroyo J, Berriman M, Abe K, Archer DB, Bermejo C, Bennett J, Bowyer P, Chen D, Collins M, Coulsen R, Davies R, Dyer PS, Farman M, Fedorova N, Feldblyum TV, Fischer R, Fosker N, Fraser A, Garcia JL, Garcia MJ, Goble A, Goldman GH, Gomi K, Griffith-Jones S, Gwilliam R, Haas B, Haas H, Harris D, Horiuchi H, Huang J, Humphray S, Jimenez J, Keller N, Khouri H, Kitamoto K, Kobayashi T, Konzack S, Kulkarni R, Kumagai T, Lafon A, Latge JP, Li W, Lord A, Lu C, Majoros WH, May GS, Miller BL, Mohamoud Y, Molina M, Monod M, Mouyna I, Mulligan S, Murphy L, O‘Neil S, Paulsen I, Penalva MA, Pertea M, Price C, Pritchard BL, Quail MA, Rabbinowitsch E, Rawlins N, Rajandream MA, Reichard U, Renauld H, Robson GD, Rodriguez de Cordoba S, Rodriguez-Pena JM, Ronning CM, Rutter S, Salzberg SL, Sanchez M, Sanchez-Ferrero JC, Saunders D, Seeger K, Squares R, Squares S, Takeuchi M, Tekaia F, Turner G, Vazquez de Aldana CR, Weidman J, White O, Woodward J, Yu JH, Fraser C, Galagan JE, Asai K, Machida M, Hall N, Barrell B, Denning DW (2005) Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus. Nature 438:1151–1156

    Article  CAS  PubMed  Google Scholar 

  • Nobile CJ, Mitchell AP (2006) Genetics and genomics of Candida albicans biofilm formation. Cell Microbiol 8:1382–1391

    Article  CAS  PubMed  Google Scholar 

  • Odds FC, Brown AJ, Gow NA (2003) Antifungal agents: mechanisms of action. Trends Microbiol 11:272–279

    Article  CAS  PubMed  Google Scholar 

  • Onyewu C, Blankenship JR, Del Poeta M, Heitman J (2003) Ergosterol biosynthesis inhibitors become fungicidal when combined with calcineurin inhibitors against Candida albicans, Candida glabrata, and Candida krusei. Antimicrob Agents Chemother 47:956–964

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perea S, Lopez-Ribot JL, Kirkpatrick WR, McAtee RK, Santillan RA, Martinez M, Calabrese D, Sanglard D, Patterson TF (2001) 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. Antimicrob Agents Chemother 45:2676–2684

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perlin DS (2007) Resistance to echinocandin-class antifungal drugs. Drug Resist Updat 10:121–130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Plaine A, Walker L, Da Costa G, Mora-Montes HM, McKinnon A, Gow NA, Gaillardin C, Munro CA, Richard ML (2008) Functional analysis of Candida albicans GPI-anchored proteins: roles in cell wall integrity and caspofungin sensitivity. Fungal Genet Biol FG & B 45:1404–1414

    Article  CAS  Google Scholar 

  • Polakova S, Blume C, Zarate JA, Mentel M, Jorck-Ramberg D, Stenderup J, Piskur J (2009) Formation of new chromosomes as a virulence mechanism in yeast Candida glabrata. Proc Natl Acad Sci U S A 106:2688–2693

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Posteraro B, Sanguinetti M, Sanglard D, La Sorda M, Boccia S, Romano L, Morace G, Fadda G (2003) Identification and characterization of a Cryptococcus neoformans ATP binding cassette (ABC) transporter-encoding gene, CnAFR1, involved in the resistance to fluconazole. Mol Microbiol 47:357–371

    Article  CAS  PubMed  Google Scholar 

  • Rajendran R, Mowat E, McCulloch E, Lappin DF, Jones B, Lang S, Majithiya JB, Warn P, Williams C, Ramage G (2011) Azole resistance of Aspergillus fumigatus biofilms is partly associated with efflux pump activity. Antimicrob Agents Chemother 55:2092–2097

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ramage G, Bachmann S, Patterson TF, Wickes BL, Lopez-Ribot JL (2002) Investigation of multidrug efflux pumps in relation to fluconazole resistance in Candida albicans biofilms. J Antimicrob Chemother 49:973–980

    Article  CAS  PubMed  Google Scholar 

  • Rex JH, Pfaller MA (2002) Has antifungal susceptibility testing come of age? Clin Infect Dis 35:982–989

    Article  CAS  PubMed  Google Scholar 

  • Ricardo E, Costa-de-Oliveira S, Dias AS, Guerra J, Rodrigues AG, Pina-Vaz C (2009) Ibuprofen reverts antifungal resistance on Candida albicans showing overexpression of CDR genes. FEMS Yeast Res 9:618–625

    Article  CAS  PubMed  Google Scholar 

  • Rodero L, Mellado E, Rodriguez AC, Salve A, Guelfand L, Cahn P, Cuenca-Estrella M, Davel G, Rodriguez-Tudela JL (2003) G484S amino acid substitution in lanosterol 14-alpha demethylase (ERG11) is related to fluconazole resistance in a recurrent Cryptococcus neoformans clinical isolate. Antimicrob Agents Chemother 47:3653–3656

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rustad TR, Stevens DA, Pfaller MA, White TC (2002) Homozygosity at the Candida albicans MTL locus associated with azole resistance. Microbiology 148:1061–1072

    Article  CAS  PubMed  Google Scholar 

  • Saidane S, Weber S, De Deken X, St-Germain G, Raymond M (2006) PDR16-mediated azole resistance in Candida albicans. Mol Microbiol 60:1546–1562

    Article  CAS  PubMed  Google Scholar 

  • Sanglard D, Kuchler K, Ischer F, Pagani JL, Monod M, Bille J (1995) Mechanisms of resistance to azole antifungal agents in Candida albicans isolates from AIDS patients involve specific multidrug transporters. Antimicrob Agents Chemother 39:2378–2386

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sanglard D, Ischer F, Bille J (2001) Role of ATP-binding-cassette transporter genes in high-frequency acquisition of resistance to azole antifungals in Candida glabrata. Antimicrob Agents Chemother 45:1174–1183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sanglard D, Ischer F, Parkinson T, Falconer D, Bille J (2003) Candida albicans mutations in the ergosterol biosynthetic pathway and resistance to several antifungal agents. Antimicrob Agents Chemother 47:2404–2412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sasaki E, Maesaki S, Miyazaki Y, Yanagihara K, Tomono K, Tashiro T, Kohno S (2000) Synergistic effect of ofloxacin and fluconazole against azole-resistant Candida albicans. J Infect Chemother 6:151–154

    Article  CAS  PubMed  Google Scholar 

  • Sasse C, Schillig R, Dierolf F, Weyler M, Schneider S, Mogavero S, Rogers PD, Morschhauser J (2011) The transcription factor Ndt80 does not contribute to Mrr1-, Tac1-, and Upc2-mediated fluconazole resistance in Candida albicans. PLoS One 6:e25623

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sasse C, Dunkel N, Schafer T, Schneider S, Dierolf F, Ohlsen K, Morschhauser J (2012) The stepwise acquisition of fluconazole resistance mutations causes a gradual loss of fitness in Candida albicans. Mol Microbiol 86:539–556

    Article  CAS  PubMed  Google Scholar 

  • Schubert S, Rogers PD, Morschhauser 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schubert S, Barker KS, Znaidi S, Schneider S, Dierolf F, Dunkel N, Aid M, Boucher G, Rogers PD, Raymond M, Morschhauser J (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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schuetzer-Muehlbauer M, Willinger B, Egner R, Ecker G, Kuchler K (2003) Reversal of antifungal resistance mediated by ABC efflux pumps from Candida albicans functionally expressed in yeast. Int J Antimicrob Agents 22:291–300

    Article  CAS  PubMed  Google Scholar 

  • Schulte TW, Akinaga S, Soga S, Sullivan W, Stensgard B, Toft D, Neckers LM (1998) Antibiotic radicicol binds to the N-terminal domain of Hsp90 and shares important biologic activities with geldanamycin. Cell Stress Chaperones 3:100–108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Selmecki A, Forche A, Berman J (2006) Aneuploidy and isochromosome formation in drug-resistant Candida albicans. Science 313:367–370

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seneviratne CJ, Wang Y, Jin L, Abiko Y, Samaranayake LP (2009) Proteomics of drug resistance in Candida glabrata biofilms. Proteomics 10:1444–1454

    Article  CAS  Google Scholar 

  • Shianna KV, Dotson WD, Tove S, Parks LW (2001) Identification of a UPC2 homolog in Saccharomyces cerevisiae and its involvement in aerobic sterol uptake. J Bacteriol 183:830–834

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shinde RB, Chauhan NM, Raut JS, Karuppayil SM (2012) Sensitization of Candida albicans biofilms to various antifungal drugs by cyclosporine A. Ann Clin Microbiol Antimicrob 11:27

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Silver PM, Oliver BG, White TC (2004) Role of Candida albicans transcription factor Upc2p in drug resistance and sterol metabolism. Eukaryot Cell 3:1391–1397

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Singh SD, Robbins N, Zaas AK, Schell WA, Perfect JR, Cowen LE (2009) Hsp90 governs echinocandin resistance in the pathogenic yeast Candida albicans via calcineurin. PLoS Pathog 5:e1000532

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sionov E, Lee H, Chang YC, Kwon-Chung KJ (2010) Cryptococcus neoformans overcomes stress of azole drugs by formation of disomy in specific multiple chromosomes. PLoS Pathog 6:e1000848

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Slaven JW, Anderson MJ, Sanglard D, Dixon GK, Bille J, Roberts IS, Denning DW (2002) Increased expression of a novel Aspergillus fumigatus ABC transporter gene, atrF, in the presence of itraconazole in an itraconazole resistant clinical isolate. Fungal Genet Biol 36:199–206

    Article  CAS  PubMed  Google Scholar 

  • Snelders E, van der Lee HA, Kuijpers J, Rijs AJ, Varga J, Samson RA, Mellado E, Donders AR, Melchers WJ, Verweij PE (2008) Emergence of azole resistance in Aspergillus fumigatus and spread of a single resistance mechanism. PLoS Med 5:e219

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Snelders E, Melchers WJ, Verweij PE (2011) Azole resistance in Aspergillus fumigatus: a new challenge in the management of invasive aspergillosis? Future Microbiol 6:335–347

    Article  CAS  PubMed  Google Scholar 

  • Snelders E, Camps SM, Karawajczyk A, Schaftenaar G, Kema GH, van der Lee HA, Klaassen CH, Melchers WJ, Verweij PE (2012) Triazole fungicides can induce cross-resistance to medical triazoles in Aspergillus fumigatus. PLoS One 7:e31801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sokol-Anderson ML, Brajtburg J, Medoff G (1986) Amphotericin B-induced oxidative damage and killing of Candida albicans. J Infect Dis 154:76–83

    Article  CAS  PubMed  Google Scholar 

  • Stebbins CE, Russo AA, Schneider C, Rosen N, Hartl FU, Pavletich NP (1997) Crystal structure of an Hsp90-geldanamycin complex: targeting of a protein chaperone by an antitumor agent. Cell 89:239–250

    Article  CAS  PubMed  Google Scholar 

  • Stevens DA, Espiritu M, Parmar R (2004) Paradoxical effect of caspofungin: reduced activity against Candida albicans at high drug concentrations. Antimicrob Agents Chemother 48:3407–3411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stevens DA, Ichinomiya M, Koshi Y, Horiuchi H (2006) Escape of Candida from caspofungin inhibition at concentrations above the MIC (paradoxical effect) accomplished by increased cell wall chitin; evidence for beta-1,6-glucan synthesis inhibition by caspofungin. Antimicrob Agents Chemother 50:3160–3161

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tanabe K, Lamping E, Adachi K, Takano Y, Kawabata K, Shizuri Y, Niimi M, Uehara Y (2007) Inhibition of fungal ABC transporters by unnarmicin A and unnarmicin C, novel cyclic peptides from marine bacterium. Biochem Biophys Res Commun 364:990–995

    Article  CAS  PubMed  Google Scholar 

  • Torelli R, Posteraro B, Ferrari S, La Sorda M, Fadda G, Sanglard D, Sanguinetti M (2008) The ATP-binding cassette transporter-encoding gene CgSNQ2 is contributing to the CgPDR1-dependent azole resistance of Candida glabrata. Mol Microbiol 68:186–201

    Article  CAS  PubMed  Google Scholar 

  • Tsai HF, Bard M, Izumikawa K, Krol AA, Sturm AM, Culbertson NT, Pierson CA, Bennett JE (2004) Candida glabrata erg1 mutant with increased sensitivity to azoles and to low oxygen tension. Antimicrob Agents Chemother 48:2483–2489

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tsai HF, Krol AA, Sarti KE, Bennett JE (2006) Candida glabrata PDR1, a transcriptional regulator of a pleiotropic drug resistance network, mediates azole resistance in clinical isolates and petite mutants. Antimicrob Agents Chemother 50:1384–1392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vandeputte P, Tronchin G, Larcher G, Ernoult E, Berges T, Chabasse D, Bouchara JP (2008) A nonsense mutation in the ERG6 gene leads to reduced susceptibility to polyenes in a clinical isolate of Candida glabrata. Antimicrob Agents Chemother 52:3701–3709

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Venkateswarlu K, Denning DW, Kelly SL (1997) Inhibition and interaction of cytochrome P450 of Candida krusei with azole antifungal drugs. J Med Vet Mycol 35:19–25

    Article  CAS  PubMed  Google Scholar 

  • Verweij PE, Snelders E, Kema GH, Mellado E, Melchers WJ (2009) Azole resistance in Aspergillus fumigatus: a side-effect of environmental fungicide use? Lancet Infect Dis 9:789–795

    Article  CAS  PubMed  Google Scholar 

  • Warrilow AG, Parker JE, Kelly DE, Kelly SL (2013) Azole affinity of sterol 14alpha-demethylase (CYP51) enzymes from Candida albicans and Homo sapiens. Antimicrob Agents Chemother 57:1352–1360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Watson PF, Rose ME, Ellis SW, England H, Kelly SL (1989) Defective sterol C5-6 desaturation and azole resistance: a new hypothesis for the mode of action of azole antifungals. Biochem Biophys Res Commun 164:1170–1175

    Article  CAS  PubMed  Google Scholar 

  • White TC, Marr KA, Bowden RA (1998) Clinical, cellular, and molecular factors that contribute to antifungal drug resistance. Clin Microbiol Rev 11:382–402

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wilcox LJ, Balderes DA, Wharton B, Tinkelenberg AH, Rao G, Sturley SL (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

    Article  CAS  PubMed  Google Scholar 

  • Willger SD, Puttikamonkul S, Kim KH, Burritt JB, Grahl N, Metzler LJ, Barbuch R, Bard M, Lawrence CB, Cramer RA Jr (2008) A sterol-regulatory element binding protein is required for cell polarity, hypoxia adaptation, azole drug resistance, and virulence in Aspergillus fumigatus. PLoS Pathog 4:e1000200

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Xiong Q, Hassan SA, Wilson WK, Han XY, May GS, Tarrand JJ, Matsuda SP (2005) Cholesterol import by Aspergillus fumigatus and its influence on antifungal potency of sterol biosynthesis inhibitors. Antimicrob Agents Chemother 49:518–524

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zavrel M, Hoot SJ, White TC (2013) Comparison of sterol import under aerobic and anaerobic conditions in three fungal species, Candida albicans, Candida glabrata, and Saccharomyces cerevisiae. Eukaryot Cell 12:725–738

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang H, Gao A, Li F, Zhang G, Ho HI, Liao W (2009) Mechanism of action of tetrandrine, a natural inhibitor of Candida albicans drug efflux pumps. Yakugaku Zasshi 129:623–630

    Article  CAS  PubMed  Google Scholar 

  • Znaidi S, De Deken X, Weber S, Rigby T, Nantel A, Raymond M (2007) The zinc cluster transcription factor Tac1p regulates PDR16 expression in Candida albicans. Mol Microbiol 66:440–452

    Article  CAS  PubMed  Google Scholar 

  • Znaidi S, Weber S, Al-Abdin OZ, Bomme P, Saidane S, Drouin S, Lemieux S, De Deken X, Robert F, Raymond M (2008) Genomewide location analysis of Candida albicans Upc2p, a regulator of sterol metabolism and azole drug resistance. Eukaryot Cell 7:836–847

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Organic Chemistry and Biochemistry, Flemingovo namesti 2, Prague 6, 166 10, Czech Republic

    Martin Zavrel

  2. Division of Cell Biology and Biophysics, School of Biological Sciences, University of Missouri-Kansas City, 5007 Rockhill Road, BSB 404, Kansas City, MO, 64110, USA

    Brooke D. Esquivel & Theodore C. White

Authors
  1. Martin Zavrel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Brooke D. Esquivel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Theodore C. White
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Theodore C. White .

Editor information

Editors and Affiliations

  1. Department of Microbiology and Immunology, McGill University, Montreal, Québec, Canada

    Albert Berghuis

  2. Department of Microbiology and Immunology, McGill University, Montreal, Québec, Canada

    Greg Matlashewski

  3. Department of Microbiology and Immunology, McGill University, Montreal, Québec, Canada

    Mark A. Wainberg

  4. Department of Microbiology and Immunology, McGill University, Montreal, Québec, Canada

    Donald Sheppard

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Science+Business Media New York

About this entry

Cite this entry

Zavrel, M., Esquivel, B.D., White, T.C. (2017). The Ins and Outs of Azole Antifungal Drug Resistance: Molecular Mechanisms of Transport. In: Berghuis, A., Matlashewski, G., Wainberg, M., Sheppard, D. (eds) Handbook of Antimicrobial Resistance. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0694-9_29

Download citation

Publish with us

Policies and ethics

Search

Navigation