ArticleAntimicrobial agents and chemotherapy2015
Contribution of clinically derived mutations in ERG11 to azole resistance in Candida albicans.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 162 papers.
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162 citing papers in PubMed, 290 citations in OpenAlex.
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- Genetic variation and mutational determinants of azole resistance in Candida albicans strains of oropharyngeal colonization in HIV patients and bloodstream infections.Journal of biomedical science · 2026Article
- Epimutations driven by RNAi or heterochromatin evoke transient antimicrobial drug resistance in pathogenic Mucor fungi.PLoS biology · 2026Article
- Recurrent mutations in the stress regulator Cap1 reveal a trade-off between azole resistance and oxidative stress response in Candida albicans.PLoS biology · 2026Article
- Molecular Identification and Evaluation of Resistance to Antifungal Drugs inHealth science reports · 2026Article
- Phylogenomic analysis and genetic mechanisms of antifungal resistance in clinical isolates ofMicrobiology spectrum · 2026Article
- Advances in vulvovaginal candidiasis research: a comprehensive review from epidemiology, diagnosis, treatment to resistance mechanisms.Frontiers in microbiology · 2026Review
- In Silico Evaluation of Acalypha indica Phytochemicals as Potential Antifungal Agents Targeting Saccharomyces cerevisiae Lanosterol 14-Alpha Demethylase.Cell biochemistry and biophysics · 2025Article
- Non-albicans Candida in Vulvovaginal Candidiasis: Antifungal Resistance and Expression of ERG11, CDR1, CDR2, and MDR1 Genes.MicrobiologyOpen · 2025Article
- Epimutations driven by RNAi or heterochromatin evoke transient antimicrobial drug resistance in fungi.bioRxiv : the preprint server for biology · 2025Article
- Community-Onset Fungemias: Epidemiology and Genomic Characterization at a Tertiary-Care Hospital in Barcelona, Spain.Journal of fungi (Basel, Switzerland) · 2025Article
- Antifungal resistance: Emerging mechanisms and implications (Review).Molecular medicine reports · 2025Review
102 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
In Candida albicans, the ERG11 gene encodes lanosterol demethylase, the target of the azole antifungals. Mutations in ERG11 that result in an amino acid substitution alter the abilities of the azoles to bind to and inhibit Erg11, resulting in resistance. Although ERG11 mutations have been observed in clinical isolates, the specific contributions of individual ERG11 mutations to azole resistance in C. albicans have not been widely explored. We sequenced ERG11 in 63 fluconazole (FLC)-resistant clinical isolates. Fifty-five isolates carried at least one mutation in ERG11, and we observed 26 distinct positions in which amino acid substitutions occurred. We mapped the 26 distinct variant positions in these alleles to four regions in the predicted structure for Erg11, including its predicted catalytic site, extended fungus-specific external loop, proximal surface, and proximal surface-to-heme region. In total, 31 distinct ERG11 alleles were recovered, with 10 ERG11 alleles containing a single amino acid substitution. We then characterized 19 distinct ERG11 alleles by introducing them into the wild-type azole-susceptible C. albicans SC5314 strain and testing them for susceptibilities to FLC, itraconazole (ITC), and voriconazole (VRC). The strains that were homozygous for the single amino acid substitutions Y132F, K143R, F145L, S405F, D446E, G448E, F449V, G450E, and G464S had a ≥ 4-fold increase in FLC MIC. The strains that were homozygous for several double amino acid substitutions had decreased azole susceptibilities beyond those conferred by any single amino acid substitution. These findings indicate that mutations in ERG11 are prevalent among azole-resistant clinical isolates and that most mutations result in appreciable changes in FLC and VRC susceptibilities.
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