Trial reportAntimicrobial agents and chemotherapy2005
Specific substitutions in the echinocandin target Fks1p account for reduced susceptibility of rare laboratory and clinical Candida sp. isolates.
Trial report in Antimicrobial agents and chemotherapy, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 216 papers.
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Who cites it
216 citing papers in PubMed, 427 citations in OpenAlex.
- Whole genome sequencing analysis of Candida glabrata isolates collected from patients with selected drug-resistant candidiasis hospitalized in Eastern Poland.Folia microbiologica · 2026Article
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- Genomic Insights ofOpen forum infectious diseases · 2026Review
- An update on clinically relevant, rare, and emergingClinical microbiology reviews · 2025Review
- A Candidozyma (Candida) auris-Optimized Episomal Plasmid-Induced Cas9-Editing System Reveals the Direct Impact of the S639F-Encoding FKS1 Mutation.The Journal of infectious diseases · 2025Article
- Hotspot gene conversion between FKS1 and FKS2 in echinocandin resistant Candida glabrata serial isolates.npj antimicrobials and resistance · 2025Article
- Anidulafungin is a useful surrogate marker for predictingJournal of clinical microbiology · 2025Article
- Ethical bioprospecting and microbial assessments for sustainable solutions to the AMR crisis.IUBMB life · 2025Review
- Resistance Mechanisms of Plant Pathogenic Fungi to Fungicide, Environmental Impacts of Fungicides, and Sustainable Solutions.Plants (Basel, Switzerland) · 2024Review
- Transposon-sequencing (Tn-seq) of the Candida glabrata reference strain CBS138 reveals epigenetic plasticity, structural variation, and intrinsic mechanisms of resistance to micafungin.G3 (Bethesda, Md.) · 2024Article
- Allosteric inhibition of tRNA synthetase Gln4 by N-pyrimidinyl-β-thiophenylacrylamides exerts highly selective antifungal activity.Cell chemical biology · 2024Article
- Genomic epidemiology of antifungal resistance in human and avian isolates ofFrontiers in veterinary science · 2024Article
- Review
- The Microevolution of Antifungal Drug Resistance in Pathogenic Fungi.Microorganisms · 2023Review
- Development of Echinocandin Resistance inJournal of fungi (Basel, Switzerland) · 2023Article
- Rapid Evolution of Multidrug Resistance in a Candida lusitaniae Infection during Micafungin Monotherapy.Antimicrobial agents and chemotherapy · 2023Article
- Review
- Genome-Wide DNA Changes Acquired byMicroorganisms · 2023Article
156 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
An association between reduced susceptibility to echinocandins and changes in the 1,3-beta-d-glucan synthase (GS) subunit Fks1p was investigated. Specific mutations in fks1 genes from Saccharomyces cerevisiae and Candida albicans mutants are described that are necessary and sufficient for reduced susceptibility to the echinocandin drug caspofungin. One group of amino acid changes in ScFks1p, ScFks2p, and CaFks1p defines a conserved region (Phe 641 to Asp 648 of CaFks1p) in the Fks1 family of proteins. The relationship between several of these fks1 mutations and the phenotype of reduced caspofungin susceptibility was confirmed using site-directed mutagenesis or integrative transformation. Glucan synthase activity from these mutants was less susceptible to caspofungin inhibition, and heterozygous and homozygous Cafks1 C. albicans mutants could be distinguished based on the shape of inhibition curves. The C. albicans mutants were less susceptible to caspofungin than wild-type strains in a murine model of disseminated candidiasis. Five Candida isolates with reduced susceptibility to caspofungin were recovered from three patients enrolled in a clinical trial. Four C. albicans strains showed amino acid changes at Ser 645 of CaFks1p, while a single Candida krusei isolate had a deduced R1361G substitution. The clinical C. albicans mutants were less susceptible to caspofungin in the disseminated candidiasis model, and GS inhibition profiles and DNA sequence analyses were consistent with a homozygous fks1 mutation. Our results indicate that substitutions in the Fks1p subunit of GS are sufficient to confer reduced susceptibility to echinocandins in S. cerevisiae and the pathogens C. albicans and C. krusei.
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