The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.
An A643V Amino Acid Substitution in Upc2p Contributes to Azole Resistance in Well-Characterized Clinical Isolates of Candida albicans
Open accessAbstract
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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In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“UPC2 mutations in C. albicans have been found in multiple clinical strains and appear to be much more commonly isolated [23,24].”
From The Candida glabrata Upc2A transcription factor is a global regulator of antifungal drug resistance pathways (2021) · cites this paper as [24]
In the citing paper
“As with the zinc cluster transcription factors Tac1 and Mrr1, gain-of-function mutations in Upc2 were found to lead to increased gene expression of ERG11 conferring fluconazole resistance in clinical isolates (Figure 2c).109 , 112–114”
From Molecular and genetic basis of azole antifungal resistance in the opportunistic pathogenic fungus Candida albicans (2020) · cites this paper as [113]
Citations
Cites
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
White, T. C. (1997) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.41.7.1482 · Cited by 612
Self-citationResistance Mechanisms in Clinical Isolates of Candida albicans
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
Self-citationCoste, 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
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
Dunkel, N., Blaß, J., Rogers, P. D., & Morschhäuser, J. (2008) · Molecular Microbiology · doi:10.1111/j.1365-2958.2008.06309.x · Cited by 278
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
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
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
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
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Hube, B., & Brunke, S. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.735022480.793557943
Metadata
- 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
- 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
- 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 › Plant Science › 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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