ArticleThe Journal of antimicrobial chemotherapy2015
Stepwise emergence of azole, echinocandin and amphotericin B multidrug resistance in vivo in Candida albicans orchestrated by multiple genetic alterations.
Article in The Journal of antimicrobial chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 89 citations in OpenAlex.
- Micafungin exposure drives multidrug resistance inbioRxiv : the preprint server for biology · 2026Article
- Deciphering the multidrug resistance paradigm inAntimicrobial agents and chemotherapy · 2026Review
- Synergistic Antifungal Effects of Honokiol and Fluconazole Against Oral Candida: Implications for Managing Drug-Resistant Infections.Clinical and experimental dental research · 2026Article
- Species Identification, Virulence Factors, and Antifungal Resistance in ClinicalMicroorganisms · 2026Article
- "Pour some sugar on me"-Environmental Candida albicans isolates and the evolution of increased pathogenicity and antifungal resistance through sugar adaptation.PLoS pathogens · 2025Article
- FungAMR: a comprehensive database for investigating fungal mutations associated with antimicrobial resistance.Nature microbiology · 2025Article
- Heterogeneity ofMicrobiology spectrum · 2025Article
- Aspergillosis: A comprehensive review of pathogenesis, drug resistance, and emerging therapeutics.Journal of food and drug analysis · 2025Review
- Genetic engineering in diatoms: advances and prospects.The Plant journal : for cell and molecular biology · 2025Review
- Candida auris MIC testing by EUCAST and clinical and laboratory standards institute broth microdilution, and gradient diffusion strips; to be or not to be amphotericin B resistant?Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases · 2025Article
- New antifungal strategies and drug development against WHO critical priority fungal pathogens.Frontiers in cellular and infection microbiology · 2025Review
- Comparative pharmacodynamics and dose optimization of liposomal amphotericin B againstAntimicrobial agents and chemotherapy · 2024Article
- Insights from Three Pan-European Multicentre Studies on Invasive Candida Infections and Outlook to ECMM Candida IV.Mycopathologia · 2024Review
- Review
- Hsp90-Mediated Multi-Drug Resistance in DNA Polymerase-Defective Strains ofJournal of fungi (Basel, Switzerland) · 2024Article
- Defining Optimal Doses of Liposomal Amphotericin B Against Candida auris: Data From an In Vitro Pharmacokinetic/Pharmacodynamic Model.The Journal of infectious diseases · 2024Article
- Repurposing a human acetyl-CoA carboxylase inhibitor firsocostat to treat fungal candidiasis alone and in combination.Antimicrobial agents and chemotherapy · 2024Article
- Molecular and Clinical Features of Fluconazole Non-susceptibleAnnals of laboratory medicine · 2023Article
- Review
- Whole-Genome Sequence Analysis ofJournal of fungi (Basel, Switzerland) · 2023Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
objectivesThe objective of this study was to characterize the underlying molecular mechanisms in consecutive clinical Candida albicans isolates from a single patient displaying stepwise-acquired multidrug resistance.
methodsNine clinical isolates (P-1 to P-9) were susceptibility tested by EUCAST EDef 7.2 and Etest. P-4, P-5, P-7, P-8 and P-9 were available for further studies. Relatedness was evaluated by MLST. Additional genes were analysed by sequencing (including FKS1, ERG11, ERG2 and TAC1) and gene expression by quantitative PCR (CDR1, CDR2 and ERG11). UV-spectrophotometry and GC-MS were used for sterol analyses. In vivo virulence was determined in the insect model Galleria mellonella and evaluated by log-rank Mantel-Cox tests.
resultsP-1 + P-2 were susceptible, P-3 + P-4 fluconazole resistant, P-5 pan-azole resistant, P-6 + P-7 pan-azole and echinocandin resistant and P-8 + P-9 MDR. MLST supported genetic relatedness among clinical isolates. P-4 harboured four changes in Erg11 (E266D, G307S, G450E and V488I), increased expression of ERG11 and CDR2 and a change in Tac1 (R688Q). P-5, P-7, P-8 and P-9 had an additional change in Erg11 (A61E), increased expression of CDR1, CDR2 and ERG11 (except for P-7) and a different amino acid change in Tac1 (R673L). Echinocandin-resistant isolates harboured the Fks1 S645P alteration. Polyene-resistant P-8 + P-9 lacked ergosterol and harboured a frameshift mutation in ERG2 (F105SfsX23). Virulence was attenuated (but equivalent) in the clinical isolates, but higher than in the azole- and echinocandin-resistant unrelated control strain.
conclusionsC. albicans demonstrates a diverse capacity to adapt to antifungal exposure. Potentially novel resistance-inducing mutations in TAC1, ERG11 and ERG2 require independent validation.
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