ArticleAntimicrobial agents and chemotherapy2014
Positions and numbers of FKS mutations in Candida albicans selectively influence in vitro and in vivo susceptibilities to echinocandin treatment.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 67 citations in OpenAlex.
- Mutational landscape and molecular bases of echinocandin resistance in Saccharomyces cerevisiae.Genetics · 2026Article
- Integrated Genomic and Phenotypic Analyses Reveal Convergent Resistance Patterns in Clinical Candida tropicalis Isolates.Mycoses · 2026Article
- Antifungal resistance: Emerging mechanisms and implications (Review).Molecular medicine reports · 2025Review
- Comparative evaluation of antifungal susceptibility testing methods of invasive Candida species and detection of FKS genes mutations in caspofungin intermediate and resistant isolates.BMC infectious diseases · 2025Article
- A synthetic peptide mimic kills Candida albicans and synergistically prevents infection.Nature communications · 2024Article
- Molecular Diagnostics for Invasive Fungal Diseases: Current and Future Approaches.Journal of fungi (Basel, Switzerland) · 2024Review
- Article
- The Microevolution of Antifungal Drug Resistance in Pathogenic Fungi.Microorganisms · 2023Review
- Development of Echinocandin Resistance inJournal of fungi (Basel, Switzerland) · 2023Article
- Caspofungin resistance in Candida albicans: genetic factors and synergistic compounds for combination therapies.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2022Review
- Molecular mechanisms of acquired antifungal drug resistance in principal fungal pathogens and EUCAST guidance for their laboratory detection and clinical implications.The Journal of antimicrobial chemotherapy · 2022Review
- Echinocandins Susceptibility Patterns of 2,787 Yeast Isolates: Importance of the Thresholds for the Detection of FKS Mutations.Antimicrobial agents and chemotherapy · 2022Article
- Antimicrobial, antioxidant and antileishmanial activities of Ziziphus lotus leaves.Archives of microbiology · 2022Article
- The Antifungal Pipeline: Fosmanogepix, Ibrexafungerp, Olorofim, Opelconazole, and Rezafungin.Drugs · 2021Review
- Sphingolipid Inhibitors as an Alternative to Treat Candidiasis Caused by Fluconazole-Resistant Strains.Pathogens (Basel, Switzerland) · 2021Article
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- Sterol 14α-Demethylase Ligand-Binding Pocket-Mediated Acquired and Intrinsic Azole Resistance in Fungal Pathogens.Journal of fungi (Basel, Switzerland) · 2020Review
- Minimal Inhibitory Concentration (MIC)-Phenomena inJournal of fungi (Basel, Switzerland) · 2019Article
- Molecular Analysis of Resistance and Detection of Non-Wild-Type Strains Using Etest Epidemiological Cutoff Values for Amphotericin B and Echinocandins for Bloodstream Candida Infections from a Tertiary Hospital in Qatar.Antimicrobial agents and chemotherapy · 2018Article
- Overcoming the Resistance Hurdle: Pharmacokinetic-Pharmacodynamic Target Attainment Analyses for Rezafungin (CD101) against Candida albicans and Candida glabrata.Antimicrobial agents and chemotherapy · 2018Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
Candidemia is the fourth most common kind of microbial bloodstream infection, with Candida albicans being the most common causative species. Echinocandins are employed as the first-line treatment for invasive candidiasis until the fungal species is determined and confirmed by clinical diagnosis. Echinocandins block the FKS glucan synthases responsible for embedding β-(1,3)-d-glucan in the cell wall. The increasing use of these drugs has led to the emergence of antifungal resistance, and elevated MICs have been associated with single-residue substitutions in specific hot spot regions of FKS1 and FKS2. Here, we show for the first time the caspofungin-mediated in vivo selection of a double mutation within one allele of the FKS1 hot spot 1 in a clinical isolate. We created a set of isogenic mutants and used a hematogenous murine model to evaluate the in vivo outcomes of echinocandin treatment. Heterozygous and homozygous double mutations significantly enhance the in vivo resistance of C. albicans compared with the resistance seen with heterozygous single mutations. The various FKS1 hot spot mutations differ in the degree of their MIC increase, substance-dependent in vivo response, and impact on virulence. Our results demonstrate that echinocandin EUCAST breakpoint definitions correlate with the in vivo response when a standard dosing regimen is used but cannot predict the in vivo response after a dose escalation. Moreover, patients colonized by a C. albicans strain with multiple mutations in FKS1 have a higher risk for therapeutic failure.
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