An A643V Amino Acid Substitution in Upc2p Contributes to Azole Resistance in Well-Characterized Clinical Isolates of Candida albicans

Hoot, Samantha J.; Smith, Adam R.; Brown, Ryan P.; White, Theodore C.

doi:10.1128/aac.00995-10

Cited by 107Antifungal resistance and susceptibilityFungal and yeast genetics researchFungal Plant Pathogen Control

An A643V Amino Acid Substitution in Upc2p Contributes to Azole Resistance in Well-Characterized Clinical Isolates of Candida albicans

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Hoot, Samantha J., Smith, Adam R., Brown, Ryan P., White, Theodore C.·2011·Antimicrobial Agents and Chemotherapy

DOI 10.1128/aac.00995-10PMC PMC3028767

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Abstract

The Candida albicans Upc2p transcription factor regulates ERG11, encoding the target of azole drugs. Gain-of-function mutations that contribute to resistance were recently identified in a series of sequential clinical isolates (N. Dunkel, T. T. Liu, K. S. Barker, R. Homayouni, J. Morschhauser, and P. D. Rogers, Eukaryot. Cell 7:1180-1190, 2008). In the present study, UPC2 was sequenced from a matched set of 17 isolates. An A643V substitution was present in all of the isolates in the series that overexpressed ERG11. Azole susceptibility, ergosterol levels, and expression of ERG genes were elevated in the A643V clinical isolates and in reconstructed strains.

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Over the past 20 years, these strains have been extensively investigated at the genomic and transcriptomic levels to elucidate the mechanisms of resistance, revealing a combination of various resistance mechanisms among the resistant strains.
“Over the past 20 years, these strains have been extensively investigated at the genomic and transcriptomic levels to elucidate the mechanisms of resistance (25–35), revealing a combination of various resistance mechanisms among the resistant strains (Table 1).”
From Potential role of lysine acetylation in the stepwise adaptation of Candida albicans to fluconazole (2025) · cites this paper as [31]
The three documented Upc2 substitutions have been identified in fluconazole-resistant clinical isolates of genetically matched isolate pairs.
“In all cases, these substitutions have been identified in fluconazoleresistant clinical isolates of genetically matched isolate pairs.”
From Gain-of-Function Mutations in UPC2 Are a Frequent Cause of ERG11 Upregulation in Azole-Resistant Clinical Isolates of Candida albicans (2012) · cites this paper as [12]
Only three Upc2 substitutions (G648D, A643T, and A643V) have been identified in clinical isolates that contribute to azole resistance.
“only three substitutions (G648D, A643T, and A643V) in Upc2 have been identified in clinical isolates that contribute to azole resistance (7, 11, 12).”
From Gain-of-Function Mutations in UPC2 Are a Frequent Cause of ERG11 Upregulation in Azole-Resistant Clinical Isolates of Candida albicans (2012) · cites this paper as [12]
Activating mutations in Upc2 result in increased expression of ERG11 and decreased fluconazole susceptibility.
“Previous studies show that activating mutations in Upc2 result in increased expression of ERG11 and decreased fluconazole susceptibility”
From Gain-of-Function Mutations in UPC2 Are a Frequent Cause of ERG11 Upregulation in Azole-Resistant Clinical Isolates of Candida albicans (2012) · cites this paper as [12]
There are no gain-of-function forms currently known for UPC2A.
“there are no gain-of-function (GOF) forms currently known for UPC2A.”
From The Candida glabrata Upc2A transcription factor is a global regulator of antifungal drug resistance pathways (2021) · cites this paper as [24]

Rapid Hypothesis Testing with Candida albicans through Gene Disruption with Short Homology Regions
Wilson, R. B., Davis, D. A., & Mitchell, A. P. (1999) · Journal of Bacteriology · doi:10.1128/jb.181.6.1868-1874.1999 · Cited by 763 · see citing works
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
White, T. C. (1997) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.41.7.1482 · Cited by 612 · see citing works
Self-citation
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White, T. C., Holleman, S., Dy, F., Mirels, L. F., & Stevens, D. A. (2002) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.46.6.1704-1713.2002 · Cited by 461 · see citing works
Self-citation
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Coste, A., Turner, V., Ischer, F., Morschhäuser, J., Forche, A., Selmecki, A., Berman, J., Bille, J., & Sanglard, D. (2006) · Genetics · doi:10.1534/genetics.105.054767 · Cited by 385 · see citing works
Quantitation of Ergosterol Content: Novel Method for Determination of Fluconazole Susceptibility of Candida albicans
Arthington-Skaggs, B. A., Jradi, H., Desai, T., & Morrison, C. J. (1999) · Journal of Clinical Microbiology · doi:10.1128/jcm.37.10.3332-3337.1999 · Cited by 365 · see citing works
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
Dunkel, N., Blaß, J., Rogers, P. D., & Morschhäuser, J. (2008) · Molecular Microbiology · doi:10.1111/j.1365-2958.2008.06309.x · Cited by 278 · see citing works
Upc2p and Ecm22p, Dual Regulators of Sterol Biosynthesis in Saccharomyces cerevisiae
Vik, Å., & Rine, J. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.19.6395-6405.2001 · Cited by 277 · see citing works
Transcriptional profiling identifies two members of the ATP-Binding cassette transporter superfamily required for sterol uptake in yeast
Wilcox, L. J., Balderes, D. A., Wharton, B., Tinkelenberg, A. H., Rao, G., & Sturley, S. L. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204707200 · Cited by 250 · see citing works
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
Dunkel, N., Liu, T. T., Barker, K. S., Homayouni, R., Morschhäuser, J., & Rogers, P. D. (2008) · Eukaryotic Cell · doi:10.1128/ec.00103-08 · Cited by 236 · see citing works
Role of Candida albicans Transcription Factor Upc2p in Drug Resistance and Sterol Metabolism
Silver, P. M., Oliver, B. G., & White, T. C. (2004) · Eukaryotic Cell · doi:10.1128/ec.3.6.1391-1397.2004 · Cited by 216 · see citing works
Self-citation
Genome-Wide Expression Profile Analysis Reveals Coordinately Regulated Genes Associated with Stepwise Acquisition of Azole Resistance in Candida albicans Clinical Isolates
Rogers, P. D., & Barker, K. S. (2003) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.47.4.1220-1227.2003 · Cited by 157 · see citing works
An A643T Mutation in the Transcription Factor Upc2p Causes Constitutive ERG11 Upregulation and Increased Fluconazole Resistance in Candida albicans
Heilmann, C. J., Schneider, S., Barker, K. S., Rogers, P. D., & Morschhäuser, J. (2010) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01102-09 · Cited by 142 · see citing works
Dual Activators of the Sterol Biosynthetic Pathway of Saccharomyces cerevisiae : Similar Activation/Regulatory Domains but Different Response Mechanisms
Davies, B. S. J., Wang, H. S., & Rine, J. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.16.7375-7385.2005 · Cited by 138 · see citing works
Heme Levels Switch the Function of Hap1 of Saccharomyces cerevisiae between Transcriptional Activator and Transcriptional Repressor
Hickman, M. J., & Winston, F. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00887-07 · Cited by 137 · see citing works
Regulatory Mechanisms Controlling Expression of the DAN/TIR Mannoprotein Genes During Anaerobic Remodeling of the Cell Wall in Saccharomyces cerevisiae
Abramova, N. E., Cohen, B. D., Sertil, O., Kapoor, R., Davies, K. J. A., & Lowry, C. V. (2001) · Genetics · doi:10.1093/genetics/157.3.1169 · Cited by 128 · see citing works
A Mutation in a Purported Regulatory Gene Affects Control of Sterol Uptake in Saccharomyces cerevisiae
Crowley, J. H., Leak, F. W., Shianna, K. V., Tove, S., & Parks, L. W. (1998) · Journal of Bacteriology · doi:10.1128/jb.180.16.4177-4183.1998 · Cited by 123 · see citing works
Genomewide Location Analysis of Candida albicans Upc2p, a Regulator of Sterol Metabolism and Azole Drug Resistance
Znaidi, S., Weber, S., Zin Al-Abdin, O., Bomme, P., Saidane, S., Drouin, S., Lemieux, S., De Deken, X., Robert, F., & Raymond, M. (2008) · Eukaryotic Cell · doi:10.1128/ec.00070-08 · Cited by 119 · see citing works
Isolation and characterization of the Saccharomyces cerevisiae SUT1 gene involved in sterol uptake
Bourot, S., & Karst, F. (1995) · Gene · doi:10.1016/0378-1119(95)00478-o · Cited by 76 · see citing works
Mot3 is a transcriptional repressor of ergosterol biosynthetic genes and is required for normal vacuolar function in Saccharomyces cerevisiae
Hongay, C., Jia, N., Bard, M., & Winston, F. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf415 · Cited by 72 · see citing works
Tetracycline alters drug susceptibility in Candida albicans and other pathogenic fungi
Oliver, B. G. G., Silver, P. M., Marie, C. S., Hoot, S. J., Leyde, S. E., & White, T. C. (2008) · Microbiology · doi:10.1099/mic.0.2007/013805-0 · Cited by 62 · see citing works
Self-citation
Cytoplasmic localization of sterol transcription factors Upc2p and Ecm22p in S. cerevisiae
Marie, C., Leyde, S., & White, T. C. (2008) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2008.07.004 · Cited by 47 · see citing works
Self-citation
Candida albicans UPC2 is transcriptionally induced in response to antifungal drugs and anaerobicity through Upc2p-dependent and -independent mechanisms
Hoot, S. J., Oliver, B. G. G., & White, T. C. (2008) · Microbiology · doi:10.1099/mic.0.2008/017475-0 · Cited by 39 · see citing works
Self-citation
Regulation of sterol metabolism in Candida albicans by the UPC2 gene
Silver, P. M., & White, T. C. (2005) · Biochemical Society Transactions · doi:10.1042/bst20051215 · Cited by 28 · see citing works
Self-citation
Regulation of sterol metabolism in Candida albicans by the UPC2 gene
White, T. C., & Silver, P. M. (2005) · Biochemical Society Transactions · doi:10.1042/bst0331215 · Cited by 19 · see citing works
Self-citation

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Whaley, S. G., Berkow, E. L., Rybak, J. M., Nishimoto, A. T., Barker, K. S., & Rogers, P. D. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.02173 · Cited by 900 · see citing works
Antifungal Drug Resistance: Molecular Mechanisms in Candida albicans and Beyond
Lee, Y., Puumala, E., Robbins, N., & Cowen, L. E. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.0c00199 · Cited by 801 · see citing works
Fluconazole resistance in Candida species: a current perspective
Berkow, E., & Lockhart, S. (2017) · Infection and Drug Resistance · doi:10.2147/idr.s118892 · Cited by 542 · see citing works
Candidiasis and Mechanisms of Antifungal Resistance
Bhattacharya, S., Sae-Tia, S., & Fries, B. C. (2020) · Antibiotics · doi:10.3390/antibiotics9060312 · Cited by 474 · see citing works
Molecular Evolution of Antifungal Drug Resistance
Robbins, N., Caplan, T., & Cowen, L. E. (2017) · Annual Review of Microbiology · doi:10.1146/annurev-micro-030117-020345 · Cited by 441 · see citing works
The Fungal CYP51s: Their Functions, Structures, Related Drug Resistance, and Inhibitors
Zhang, J., Li, L., Lv, Q., Yan, L., Wang, Y., & Jiang, Y. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.00691 · Cited by 249 · see citing works
Gain-of-Function Mutations in UPC2 Are a Frequent Cause of ERG11 Upregulation in Azole-Resistant Clinical Isolates of Candida albicans
Flowers, S. A., Barker, K. S., Berkow, E. L., Toner, G., Chadwick, S. G., Gygax, S. E., Morschhäuser, J., & Rogers, P. D. (2012) · Eukaryotic Cell · doi:10.1128/ec.00215-12 · Cited by 239 · see citing works
“Previous studies show that activating mutations in Upc2 result in increased expression of ERG11 and decreased fluconazole susceptibility; however, only three substitutions (G648D, A643T, and A643V) in Upc2 have been identified in clinical isolates that contribute to azole resistance (7, 11, 12).”
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Costa-de-Oliveira, S., & Rodrigues, A. G. (2020) · Microorganisms · doi:10.3390/microorganisms8020154 · Cited by 229 · see citing works
Structural mechanism of ergosterol regulation by fungal sterol transcription factor Upc2
Yang, H., Tong, J., Lee, C. W., Ha, S., Eom, S. H., & Im, Y. J. (2015) · Nature Communications · doi:10.1038/ncomms7129 · Cited by 223 · see citing works
Discovery of a hapE Mutation That Causes Azole Resistance in Aspergillus fumigatus through Whole Genome Sequencing and Sexual Crossing
Camps, S. M. T., Dutilh, B. E., Arendrup, M. C., Rijs, A. J. M. M., Snelders, E., Huynen, M. A., Verweij, P. E., & Melchers, W. J. G. (2012) · PLoS ONE · doi:10.1371/journal.pone.0050034 · Cited by 208 · see citing works
Global Analysis of the Evolution and Mechanism of Echinocandin Resistance in Candida glabrata
Singh-Babak, S. D., Babak, T., Diezmann, S., Hill, J. A., Xie, J. L., Chen, Y.-L., Poutanen, S. M., Rennie, R. P., Heitman, J., & Cowen, L. E. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002718 · Cited by 204 · see citing works
Molecular Mechanisms Associated with Antifungal Resistance in Pathogenic Candida Species
Czajka, K. M., Venkataraman, K., Brabant-Kirwan, D., Santi, S. A., Verschoor, C. P., Appanna, V. D., Singh, R. I., Saunders, D., & Tharmalingam, S. (2023) · Cells · doi:10.3390/cells12222655 · Cited by 196 · see citing works
Antifungals: Mechanism of Action and Drug Resistance
Prasad, R., Shah, A. H., & Rawal, M. K. (2015) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-25304-6_14 · Cited by 185 · see citing works
Regulation of Efflux Pump Expression and Drug Resistance by the Transcription Factors Mrr1, Upc2, and Cap1 in Candida albicans
Schubert, S., Barker, K. S., Znaidi, S., Schneider, S., Dierolf, F., Dunkel, N., Aïd, M., Boucher, G., Rogers, P. D., Raymond, M., et al. (2011) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01343-10 · Cited by 135 · see citing works
The development of fluconazole resistance in Candida albicans – an example of microevolution of a fungal pathogen
Morschhäuser, J. (2016) · Journal of Microbiology · doi:10.1007/s12275-016-5628-4 · Cited by 118 · see citing works
Molecular and genetic basis of azole antifungal resistance in the opportunistic pathogenic fungusCandida albicans
Nishimoto, A. T., Sharma, C., & Rogers, P. D. (2020) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkz400 · Cited by 102 · see citing works
Fungal Drug Response and Antimicrobial Resistance
Osset-Trénor, P., Pascual‐Ahuir, A., & Proft, M. (2023) · Journal of Fungi · doi:10.3390/jof9050565 · Cited by 103 · see citing works
The stepwise acquisition of fluconazole resistance mutations causes a gradual loss of fitness in <scp>C</scp>andida albicans
Sasse, C., Dunkel, N., Schäfer, T., Schneider, S., Dierolf, F., Ohlsen, K., & Morschhäuser, J. (2012) · Molecular Microbiology · doi:10.1111/j.1365-2958.2012.08210.x · Cited by 93 · see citing works
Comparison of Sterol Import under Aerobic and Anaerobic Conditions in Three Fungal Species, Candida albicans, Candida glabrata, and Saccharomyces cerevisiae
Zavrel, M., Hoot, S. J., & White, T. C. (2013) · Eukaryotic Cell · doi:10.1128/ec.00345-12 · Cited by 86 · see citing works
Self-citation
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Antifungal drug resistance in Candida species
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Fitness Trade-Offs Associated with the Evolution of Resistance to Antifungal Drug Combinations
Hill, J. A., O’Meara, T. R., & Cowen, L. E. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.01.009 · Cited by 80 · see citing works
SREBP-Dependent Triazole Susceptibility in Aspergillus fumigatus Is Mediated through Direct Transcriptional Regulation oferg11A(cyp51A)
Blosser, S. J., & Cramer, R. A. (2011) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.05027-11 · Cited by 79 · see citing works
UPC2 Is Universally Essential for Azole Antifungal Resistance in Candida albicans
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Polymerase Chain Reaction-Based Assays for the Diagnosis of Invasive Fungal Infections
Kourkoumpetis, T. K., Fuchs, B. B., Coleman, J. J., Desalermos, A. P., & Mylonakis, E. E. (2012) · Clinical Infectious Diseases · doi:10.1093/cid/cis132 · Cited by 73 · see citing works
Proteomic analysis uncovers the modulation of ergosterol, sphingolipid and oxidative stress pathway by myristic acid impeding biofilm and virulence in Candida albicans
Prasath, K. G., Sethupathy, S., & Pandian, S. K. (2019) · Journal of Proteomics · doi:10.1016/j.jprot.2019.103503 · Cited by 77 · see citing works
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Song, J., Zhang, S., & Lü, L. (2018) · Fungal Biology Reviews · doi:10.1016/j.fbr.2018.05.001 · Cited by 68 · see citing works
Resistance Mechanisms and Clinical Features of Fluconazole-Nonsusceptible Candida tropicalis Isolates Compared with Fluconazole-Less-Susceptible Isolates
Choi, M. J., Won, E. J., Shin, J. H., Kim, S. H., Lee, W. G., Kim, M., Lee, K., Shin, M., Suh, S., Ryang, D. W., et al. (2016) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02652-15 · Cited by 69 · see citing works
Exceptional Solvent Tolerance in Yarrowia lipolytica Is Enhanced by Sterols
Walker, C., Ryu, S., & Trinh, C. T. (2018) · Metabolic Engineering · doi:10.1016/j.ymben.2019.03.003 · Cited by 67 · see citing works
Understanding the mechanisms of resistance to azole antifungals in Candida species
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Linking Cellular Morphogenesis with Antifungal Treatment and Susceptibility in Candida Pathogens
Sharma, J., Rosiana, S., Razzaq, I., & Shapiro, R. S. (2019) · Journal of Fungi · doi:10.3390/jof5010017 · Cited by 64 · see citing works
Medically Important Fungi Respond to Azole Drugs: An Update
Zavřel, M., & White, T. C. (2015) · Future Microbiology · doi:10.2217/fmb.15.47 · Cited by 64 · see citing works
Self-citation
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Liu, J., Wang, S., Qin, T., Li, N., Niu, Y., Li, D., Yuan, Y., Geng, H., Li, X., & Liu, D. (2015) · BMC Genomics · doi:10.1186/s12864-015-2043-x · Cited by 62 · see citing works
Inhibition of Classical and Alternative Modes of Respiration in Candida albicans Leads to Cell Wall Remodeling and Increased Macrophage Recognition
Duvenage, L., Walker, L. A., Bojarczuk, A., Johnston, S. A., MacCallum, D. M., Munro, C. A., & Gourlay, C. W. (2019) · mBio · doi:10.1128/mbio.02535-18 · Cited by 61 · see citing works
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Sasse, C., Schillig, R., Dierolf, F., Weyler, M., Schneider, S., Mogavero, S., Rogers, P. D., & Morschhäuser, J. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025623 · Cited by 61 · see citing works
Competitive Fitness of Fluconazole-Resistant Clinical Candida albicans Strains
Popp, C., Hampe, I. A. I., Hertlein, T., Ohlsen, K., Rogers, P. D., & Morschhäuser, J. (2017) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00584-17 · Cited by 56 · see citing works
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Salazar, S. B., Simões, R., Pedro, N. A., Pinheiro, M. J. F., Carvalho, M. F. N. N., & Mira, N. P. (2020) · Journal of Fungi · doi:10.3390/jof6010023 · Cited by 55 · see citing works
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Whaley, S. G., Caudle, K. E., Vermitsky, J.-P., Chadwick, S. G., Toner, G., Barker, K. S., Gygax, S. E., & Rogers, P. D. (2014) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02217-13 · Cited by 52 · see citing works
Microevolution of the pathogenic yeasts Candida albicans and Candida glabrata during antifungal therapy and host infection
Pais, P., Galocha, M., Viana, R., Cavalheiro, M., Pereira, D., & Teixeira, M. C. (2019) · Microbial Cell · doi:10.15698/mic2019.03.670 · Cited by 52 · see citing works
Milbemycins: More than Efflux Inhibitors for Fungal Pathogens
Silva, L. V., Sanguinetti, M., Vandeputte, P., Torelli, R., Rochat, B., & Sanglard, D. (2013) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02040-12 · Cited by 49 · see citing works
An acquired mechanism of antifungal drug resistance simultaneously enables Candida albicans to escape from intrinsic host defenses
Hampe, I. A. I., Friedman, J., Edgerton, M., & Morschhäuser, J. (2017) · PLoS Pathogens · doi:10.1371/journal.ppat.1006655 · Cited by 48 · see citing works
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Song, L., Wang, S., Zou, H., Yi, X., Jia, S., Li, R., & Song, J. (2025) · Microorganisms · doi:10.3390/microorganisms13040862 · Cited by 49 · see citing works
Evolution of Fluconazole-Resistant Candida albicans Strains by Drug-Induced Mating Competence and Parasexual Recombination
Popp, C., Ramı́rez-Zavala, B., Schwanfelder, S., Krüger, I., & Morschhäuser, J. (2019) · mBio · doi:10.1128/mbio.02740-18 · Cited by 41 · see citing works
Emerging Mechanisms of Drug Resistance in Candida albicans
Prasad, R., Nair, R., & Banerjee, A. (2019) · Progress in molecular and subcellular biology · doi:10.1007/978-3-030-13035-0_6 · Cited by 43 · see citing works
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Joshua, I., & Höfken, T. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18040772 · Cited by 40 · see citing works
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The cellular and molecular defense mechanisms of the Candida yeasts against azole antifungal drugs
Noël, T. (2012) · Journal de Mycologie Médicale · doi:10.1016/j.mycmed.2012.04.004 · Cited by 40 · see citing works
Functional Dissection of a Candida albicans Zinc Cluster Transcription Factor, the Multidrug Resistance Regulator Mrr1
Schubert, S., Popp, C., Rogers, P. D., & Morschhäuser, J. (2011) · Eukaryotic Cell · doi:10.1128/ec.05100-11 · Cited by 39 · see citing works
The Candida glabrata Upc2A transcription factor is a global regulator of antifungal drug resistance pathways
Vu, B. G., Stamnes, M. A., Li, Y., Rogers, P. D., & Moye-Rowley, W. S. (2021) · PLOS Genetics · doi:10.1371/journal.pgen.1009582 · Cited by 39 · see citing works
Structural basis for activation of fungal sterol receptor Upc2 and azole resistance
Tan, L., Chen, L., Yang, H., Jin, B., Kim, G., & Im, Y. J. (2022) · Nature Chemical Biology · doi:10.1038/s41589-022-01117-0 · Cited by 38 · see citing works
ERG11 mutations associated with azole resistance in Candida albicans isolates from vulvovaginal candidosis patients
Wang, B., Huang, L., Zhao, J., Wei, M., Fang, H., Wang, D., Wang, H.-F., Yin, J., & Mei, X. (2015) · Asian Pacific Journal of Tropical Biomedicine · doi:10.1016/j.apjtb.2015.08.002 · Cited by 37 · see citing works
Resistance to antifungal therapies
Prasad, R., Banerjee, A., & Shah, A. H. (2017) · Essays in Biochemistry · doi:10.1042/ebc20160067 · Cited by 33 · see citing works
Novel Antifungal Drug Discovery Based on Targeting Pathways Regulating the Fungus-Conserved Upc2 Transcription Factor
Gallo-Ebert, C., Donigan, M., Stroke, I. L., Swanson, R. N., Manners, M. T., Francisco, J., Toner, G., Gallagher, D., Huang, C.-Y., Gygax, S. E., et al. (2014) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01677-13 · Cited by 32 · see citing works
In vitro and in vivo antifungal activities and mechanism of heteropolytungstates against Candida species
Li, H., Gong, H., Qi, Y., Li, J., Ji, X., Sun, J., Tian, R., Bao, H., Song, X., Chen, Q., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-17239-8 · Cited by 30 · see citing works
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Luna-Tapia, A., Willems, H. M. E., Parker, J. E., Tournu, H., Barker, K. S., Nishimoto, A. T., Rogers, P. D., Kelly, S. L., Peters, B. M., & Palmer, G. E. (2018) · mBio · doi:10.1128/mbio.00225-18 · Cited by 29 · see citing works
Genome sequence of the opportunistic human pathogen Magnusiomyces capitatus
Brejová, B., Lichancová, H., Brázdovič, F., Hegedűsová, E., Jakúbková, M., Hodorová, V., Džugasová, V., Baláž, A., Zeiselová, L., Cillingová, A., et al. (2018) · Current Genetics · doi:10.1007/s00294-018-0904-y · Cited by 28 · see citing works
The Role of UPC2 Gene in Azole-Resistant Candida tropicalis
Jiang, C., Ni, Q., Dong, D., Zhang, L., Li, Z., Tian, Y., & Peng, Y. (2016) · Mycopathologia · doi:10.1007/s11046-016-0050-3 · Cited by 27 · see citing works
The Microevolution of Antifungal Drug Resistance in Pathogenic Fungi
Boyce, K. J. (2023) · Microorganisms · doi:10.3390/microorganisms11112757 · Cited by 25 · see citing works
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Schneider, S., & Morschhäuser, J. (2014) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.04448-14 · Cited by 23 · see citing works
The zinc cluster proteins U pc2 and E cm22 promote filamentation in S accharomyces cerevisiae by sterol biosynthesis‐dependent and ‐independent pathways
Woods, K., & Höfken, T. (2015) · Molecular Microbiology · doi:10.1111/mmi.13244 · Cited by 23 · see citing works
Mechanisms of Candida Resistance to Antimycotics and Promising Ways to Overcome It: The Role of Probiotics
Demin, K. A., Refeld, A. G., Bogdanova, A. A., Prazdnova, E. V., Popov, I. V., Kutsevalova, O. Y., Ermakov, A. M., Bren, A. B., Rudoy, D. V., Chistyakov, V. A., et al. (2021) · Probiotics and Antimicrobial Proteins · doi:10.1007/s12602-021-09776-6 · Cited by 24 · see citing works
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Zavřel, M., Esquivel, B. D., & White, T. C. (2017) · Springer eBooks · doi:10.1007/978-1-4939-0694-9_29 · Cited by 20 · see citing works
Self-citation
Combined in vitro and in silico approach to evaluate the inhibitory potential of an underutilized allium vegetable and its pharmacologically active compounds on multidrug resistant Candida species
Nallal, V. U. M., PADMINI, R., Ravindran, B., Chang, S. W., Radhakrishnan, R., Almoallim, H. S. M., Alharbi, S. A., & Razia, M. (2020) · Saudi Journal of Biological Sciences · doi:10.1016/j.sjbs.2020.11.082 · Cited by 20 · see citing works
Ascorbic Acid Inhibition of Candida albicans Hsp90-Mediated Morphogenesis Occurs via the Transcriptional Regulator Upc2
Hauwenhuyse, F. V., Fiori, A., & Dijck, P. V. (2014) · Eukaryotic Cell · doi:10.1128/ec.00096-14 · Cited by 19 · see citing works
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Ramı́rez-Zavala, B., Manz, H., Englert, F., Rogers, P. D., & Morschhäuser, J. (2018) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01655-18 · Cited by 19 · see citing works
A Proteomic Landscape of Candida albicans in the Stepwise Evolution to Fluconazole Resistance
Song, N., Zhou, X., Li, D., Li, X., & Liu, W. (2022) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02105-21 · Cited by 17 · see citing works
Drug design strategies for the treatment azole-resistant candidiasis
Moghimi, S., Shafiei, M., & Foroumadi, A. (2022) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2022.2098949 · Cited by 13 · see citing works
Experimental and in-host evolution of triazole resistance in human pathogenic fungi
Handelman, M., & Osherov, N. (2022) · Frontiers in Fungal Biology · doi:10.3389/ffunb.2022.957577 · Cited by 14 · see citing works
Mechanisms of Drug Resistance in Fungi and Their Significance in Biofilms
Prasad, R., Shah, A. H., & Dhamgaye, S. (2014) · Springer series on biofilms · doi:10.1007/978-3-642-53833-9_4 · Cited by 13 · see citing works
The Absence of PDR16 Gene Restricts the Overexpression of CaSNQ2 Gene in the Presence of Fluconazole in Candida albicans
Bencova, A., Goffa, E., Morvová, M., Valachovič, M., Griač, P., Hervay, N. T., & Gbelská, Y. (2020) · Mycopathologia · doi:10.1007/s11046-020-00459-4 · Cited by 12 · see citing works
The Yeast Anaerobic Response Element AR1b Regulates Aerobic Antifungal Drug-dependent Sterol Gene Expression
Ebert, C., Donigan, M., Liu, H., Pascual, F. L., Manners, M. T., Pandya, D., Swanson, R., Gallagher, D., Chen, W., Carman, G. M., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.526087 · Cited by 11 · see citing works
In Vitro Anticandidal Activity and Mechanism of a Polyoxovanadate Functionalized by Zn-Fluconazole Complexes
Guo, S., Yang, W., Zhao, M., Tian, R., Zhang, B., & Qi, Y. (2018) · Molecules · doi:10.3390/molecules23051122 · Cited by 11 · see citing works
Adaptation of Candida albicans to specific host environments by gain-of-function mutations in transcription factors
Morschhäuser, J. (2024) · PLoS Pathogens · doi:10.1371/journal.ppat.1012643 · Cited by 7 · see citing works
Diagnosis of Antifungal Drug Resistance Mechanisms in Fungal Pathogens: Transcriptional Gene Regulation
Sanglard, D. (2011) · Current Fungal Infection Reports · doi:10.1007/s12281-011-0055-9 · Cited by 6 · see citing works
Biofilm Alterations on the Stepwise Acquisition of Fluconazole-resistant Candida Albicans Isolates
Song, N.-N., Qian, G.-Y., Zheng, H.-L., Zhou, X.-W., Mei, H., Li, D.-M., Li, X.-F., & Liu, W.-D. (2022) · International Journal of Dermatology and Venereology · doi:10.1097/jd9.0000000000000223 · Cited by 5 · see citing works
The Ins and Outs of Azole Antifungal Drug Resistance: Molecular Mechanisms of Transport
Zavřel, M., Esquivel, B. D., & White, T. C. (2014) · Springer eBooks · doi:10.1007/978-1-4939-0667-3_29-1 · Cited by 5 · see citing works
Self-citation
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Puumala, E., Sychantha, D., Lach, E., Reeves, S., Nabeela, S., Fogal, M., Nigam, A., Johnson, J. W., Aspuru‐Guzik, A., Shapiro, R. S., et al. (2024) · Cell chemical biology · doi:10.1016/j.chembiol.2024.01.010 · Cited by 5 · see citing works
Crystallization and preliminary X-ray crystallographic analysis of sterol transcription factor Upc2 fromSaccharomyces cerevisiae
Ha, S., Tong, J., Yang, H., Youn, H., Eom, S. H., & Im, Y. J. (2013) · Acta Crystallographica Section F Structural Biology and Crystallization Communications · doi:10.1107/s1744309112051597 · Cited by 5 · see citing works
Candida glabrata maintains two HAP1 ohnologs, HAP1A and HAP1B , for distinct roles in ergosterol gene regulation to mediate sterol homeostasis under azole and hypoxic conditions
Saha, D., Gregor, J. B., Hoda, S., Eastman, K. E., Gutierrez-Schultz, V. A., Navarrete, M., Wisecaver, J. H., & Briggs, S. D. (2024) · mSphere · doi:10.1128/msphere.00524-24 · Cited by 4 · see citing works
The zinc cluster transcription factor Znc1 regulates Rta3-dependent miltefosine resistance in Candida albicans
Ramı́rez-Zavala, B., Krüger, I., Schwanfelder, S., Barker, K. S., Rogers, P. D., & Morschhäuser, J. (2024) · mSphere · doi:10.1128/msphere.00270-24 · Cited by 5 · see citing works
Azole resistance is mediated by integration of sterol gene regulation and membrane transporter production by the zinc cluster-containing transcription factor Upc2A in Candida glabrataPreprint
Vu, B. G., Stamnes, M. A., Li, Y., Rogers, P. D., & Moye-Rowley, S. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.05.07.443069 · Cited by 4 · see citing works
Transcription factor Hap2p regulates antioxidant stress responses to maintain miconazole resistance in Candida albicans
Qin, Y., Lv, Q., Xu, H., Cao, Y., & Han, B. (2025) · Mycology&#58 An International Journal on Fungal Biology · doi:10.1080/21501203.2024.2432424 · Cited by 2 · see citing works
Antifungal Resistance in Candida albicans
Seyedjavadi, S. S., Hatami, F., & Jahanshiri, Z. (2024) · IntechOpen eBooks · doi:10.5772/intechopen.1004578 · Cited by 2 · see citing works
Microevolution of Antifungal Drug Resistance
Cowen, L. E. (2014) · Springer eBooks · doi:10.1007/978-1-4939-0667-3_19-1 · Cited by 2 · see citing works
UPC2 mutations and development of azole resistance in Candida albicans hospital isolates from Lebanon
Fattouh, N., Hdayed, D., Hijazi, A., Tokajian, S. T., & Khalaf, R. A. (2024) · Journal of Global Antimicrobial Resistance · doi:10.1016/j.jgar.2024.07.010 · Cited by 2 · see citing works
MDR1 and Its Regulation
Morschhäuser, J. (2017) · Springer eBooks · doi:10.1007/978-3-319-50409-4_19 · Cited by 1 · see citing works
Mechanisms of pathogenesis and drug resistance in Candida auris
WeiNa, Z. H. A. O., Zhang, B., & QiMing, W. A. N. G. (2021) · Scientia Sinica Vitae · doi:10.1360/ssv-2021-0230
Evolution of Drug Resistance in Fungi
Hill, J. A., Hoot, S. J., White, T. C., & Cowen, L. E. (2012) · Wiley eBooks · doi:10.1002/9781118308165.ch8 · Cited by 1 · see citing works
Self-citation
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Caplan, T. (2018) · TSpace (University of Toronto) · Cited by 1 · see citing works
Fenhexamid : mode d’action et résistance chez le complexe d’espèces Botrytis SPP., responsable de la pourriture grise de la vigne
Billard, A. (2011) · doi:10.70675/2bdede85zcc47z45bezaafbz2b104a8a77d4 · Cited by 1 · see citing works
Potential role of lysine acetylation in the stepwise adaptation of Candida albicans to fluconazole
Song, N., Huang, Y., Zhou, X., Li, D., Liu, W., & Li, X. (2025) · Microbiology Spectrum · doi:10.1128/spectrum.02797-24
SrbA-regulation of ergosterol biosynthesis in Aspergillus fumigatus: Gateway to azole resistance & hypoxia adaptation
Blosser, S. J. (2013) · Montana State University ScholarWorks (Montana State University)
Molecular mechanisms of azole resistance in Aspergillus fumigatus
Camps, S. M. T. (2013) · Radboud Repository (Radboud University)
ERG11-Mediated Azole Resistance in Candida albicans
Flowers, S. A. (2013) · doi:10.21007/etd.cghs.2013.0096
The Roles of Hsp90 and Calcineurin in Antifungal Drug Resistance
Singh, S. (2012) · TSpace (University of Toronto)
Determining the Mechanisms of Resistance to Drug Combinations and their Fitness Effects in Candida albicans
Hill, J. A. (2014) · TSpace (University of Toronto)
An Investigation into Clinically Relevant Determinants of Azole Resistance in Candida albicans
Nishimoto, A. T. (2019) · doi:10.21007/etd.cghs.2019.0486
Targeting Casein Kinases in the Fungal Pathogen Candida albicans
Hyde, S. (2020) · TSpace (University of Toronto)
The SUMO protease Ulp2 regulates genome stability and drug resistance in the human fungal pathogen Candida albicansPreprint
Rizzo, M., Soisangwan, N., Soetaert, J., Vega, S. B. P., Selmecki, A. M., & Buscaino, A. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.12.06.471441

Gain-of-Function Mutations in UPC2 Are a Frequent Cause of ERG11 Upregulation in Azole-Resistant Clinical Isolates of Candida albicans
Flowers, S. A., Barker, K. S., Berkow, E. L., Toner, G., Chadwick, S. G., Gygax, S. E., Morschhäuser, J., & Rogers, P. D. (2012) · Eukaryotic Cell · doi:10.1128/ec.00215-12 · Cited by 239 · see citing works
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
Dunkel, N., Liu, T. T., Barker, K. S., Homayouni, R., Morschhäuser, J., & Rogers, P. D. (2008) · Eukaryotic Cell · doi:10.1128/ec.00103-08 · Cited by 236 · see citing works
An A643T Mutation in the Transcription Factor Upc2p Causes Constitutive ERG11 Upregulation and Increased Fluconazole Resistance in Candida albicans
Heilmann, C. J., Schneider, S., Barker, K. S., Rogers, P. D., & Morschhäuser, J. (2010) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01102-09 · Cited by 142 · see citing works
UPC2 mutations and development of azole resistance in Candida albicans hospital isolates from Lebanon
Fattouh, N., Hdayed, D., Hijazi, A., Tokajian, S. T., & Khalaf, R. A. (2024) · Journal of Global Antimicrobial Resistance · doi:10.1016/j.jgar.2024.07.010 · Cited by 2 · see citing works
UPC2 Is Universally Essential for Azole Antifungal Resistance in Candida albicans
Vasicek, E. M., Berkow, E. L., Flowers, S. A., Barker, K. S., & Rogers, P. D. (2014) · Eukaryotic Cell · doi:10.1128/ec.00221-13 · Cited by 71 · see citing works

Authors: Hoot, S. J., Smith, A. R., Brown, R. P., & White, T. C.
Affiliations: Center for Infectious Disease Research (US)
Corresponding author: White, Theodore C.
ORCID: White, Theodore C.
Venue: Antimicrobial Agents and Chemotherapy
Publisher: American Society for Microbiology
Published: 2011-02
Volume: 55
Issue: 2
Pages: 940-942
ISSN: 0066-4804 (ISSN-L)
1098-6596
DOI: 10.1128/aac.00995-10
PMC: PMC3028767
OpenAlex: W1971071885
Cited by: 107
References: 24
Citations by year: 2026: 2 · 2025: 4 · 2024: 8 · 2023: 4 · 2022: 5 · 2021: 6 · 2020: 8 · 2019: 10 · 2018: 7 · 2017: 10 · 2016: 3 · 2015: 8 · 2014: 9 · 2013: 8 · 2012: 9
FWCI: 4.77
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Antimicrobial Agents and Chemotherapy (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
National Institute of Dental and Craniofacial Research (R01DE011367, R01DE017078, R01 DE-11367, R01 DE 14161, R01DE014161)
Topics: Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
Keywords: Candida albicans, azole resistance, ERG11, transcription factors, clinical isolates, ergosterol, antifungal resistance, gain-of-function mutations
MeSH terms: Antifungal Agents, Azoles, Candida albicans, Ergosterol, Fungal Proteins, Humans, Microbial Sensitivity Tests, Trans-Activators, Fluconazole, Gene Expression Regulation, Fungal, Sequence Analysis, DNA, Amino Acid Substitution, Drug Resistance, Fungal

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An A643V Amino Acid Substitution in Upc2p Contributes to Azole Resistance in Well-Characterized Clinical Isolates of Candida albicans

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