ArticleAntimicrobial agents and chemotherapy2009
A Ser29Leu substitution in the cytosine deaminase Fca1p is responsible for clade-specific flucytosine resistance in Candida dubliniensis.
Article in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 25 citations in OpenAlex.
- Deciphering the multidrug resistance paradigm inAntimicrobial agents and chemotherapy · 2026Review
- Resistance gene mutations and phylogenetic relationships inFrontiers in cellular and infection microbiology · 2026Article
- Genetic mutations in Cryptococcus neoformans pyrimidine salvage pathway enzymes contribute to reduced susceptibility against 5-fluorocytosine.npj antimicrobials and resistance · 2024Article
- Review
- Cross-feeding affects the target of resistance evolution to an antifungal drug.PLoS genetics · 2023Article
- Cryptococcus neoformans, a global threat to human health.Infectious diseases of poverty · 2023Review
- Molecular Mechanisms of 5-Fluorocytosine Resistance in Yeasts and Filamentous Fungi.Journal of fungi (Basel, Switzerland) · 2021Review
- 5-fluorocytosine resistance is associated with hypermutation and alterations in capsule biosynthesis in Cryptococcus.Nature communications · 2020Article
- Flucytosine resistance in Cryptococcus gattii is indirectly mediated by the FCY2-FCY1-FUR1 pathway.Medical mycology · 2018Article
- Article
- Candida infections and their prevention.ISRN preventive medicine · 2013Review
- Progress in antifungal susceptibility testing of Candida spp. by use of Clinical and Laboratory Standards Institute broth microdilution methods, 2010 to 2012.Journal of clinical microbiology · 2012Review
- Wild-type MIC distributions and epidemiological cutoff values for amphotericin B, flucytosine, and itraconazole and Candida spp. as determined by CLSI broth microdilution.Journal of clinical microbiology · 2012Article
- Candida dubliniensis: an appraisal of its clinical significance as a bloodstream pathogen.PloS one · 2012Article
- Microbiological screening of Irish patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy reveals persistence of Candida albicans strains, gradual reduction in susceptibility to azoles, and incidences of clinical signs of oral candidiasis without culture evidence.Journal of clinical microbiology · 2011Article
- Mutational analysis of flucytosine resistance in Candida glabrata.Antimicrobial agents and chemotherapy · 2010Article
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5 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
The population structure of the opportunistic yeast pathogen Candida dubliniensis is composed of three main multilocus sequence typing clades (clades C1 to C3), and clade C3 predominantly consists of isolates from the Middle East that exhibit high-level resistance (MIC(50) > or = 128 microg/ml) to the fungicidal agent flucytosine (5FC). The close relative of C. dubliniensis, C. albicans, also exhibits clade-specific resistance to 5FC, and resistance is most commonly mediated by an Arg101Cys substitution in the FUR1 gene encoding uracil phosphoribosyltransferase. Broth microdilution assays with fluorouracil (5FU), the toxic deaminated form of 5FC, showed that both 5FC-resistant and 5FC-susceptible C. dubliniensis isolates exhibited similar 5FU MICs, suggesting that the C. dubliniensis cytosine deaminase (Fca1p) encoded by C. dubliniensis FCA1 (CdFCA1) may play a role in mediating C. dubliniensis clade-specific 5FC resistance. Amino acid sequence analysis of the CdFCA1 open reading frame (ORF) identified a homozygous Ser29Leu substitution in all 12 5FC-resistant isolates investigated which was not present in any of the 9 5FC-susceptible isolates examined. The tetracycline-inducible expression of the CdFCA1 ORF from a 5FC-susceptible C. dubliniensis isolate in two separate 5FC-resistant clade C3 isolates restored susceptibility to 5FC, demonstrating that the Ser29Leu substitution was responsible for the clade-specific 5FC resistance and that the 5FC resistance encoded by FCA1 genes with the Ser29Leu transition is recessive. Quantitative real-time PCR analysis showed no significant difference in CdFCA1 expression between 5FC-susceptible and 5FC-resistant isolates in either the presence or the absence of subinhibitory concentrations of 5FC, suggesting that the Ser29Leu substitution in the CdFCA1 ORF is the sole cause of 5FC resistance in clade C3 C. dubliniensis isolates.
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