RRC ID 74262
Author Khalifa HO, Hubka V, Watanabe A, Nagi M, Miyazaki Y, Yaguchi T, Kamei K.
Title Prevalence of Antifungal Resistance, Genetic Basis of Acquired Azole and Echinocandin Resistance, and Genotyping of Candida krusei Recovered from an International Collection.
Journal Antimicrob Agents Chemother
Abstract This study was designed to evaluate the prevalence of antifungal resistance, genetic mechanisms associated with in vitro induction of azole and echinocandin resistance and genotyping of Candida krusei, which is intrinsically resistant to fluconazole and is recovered from clinical and nonclinical sources from different countries. Our results indicated that all the isolates were susceptible or had the wild phenotype (WT) to azoles, amphotericin B, and only 1.27% showed non-WT for flucytosine. Although 70.88% of the isolates were resistant to caspofungin, none of them were categorized as echinocandin-resistant as all were susceptible to micafungin and no FKS1 hot spot 1 (HS1) or HS2 mutations were detected. In vitro induction of azole and echinocandin resistance confirmed the rapid development of resistance at low concentrations of fluconazole (4 μg/ml), voriconazole (0.06 μg/ml), and micafungin (0.03 μg/ml), with no difference between clinical and nonclinical isolates in the resistance development. Overexpression of ABC1 gene and FKS1 HS1 mutations were the major mechanisms responsible for azole and echinocandin resistance, respectively. Genotyping of our 79 isolates coupled with 217 other isolates from different sources and geography confirmed that the isolates belong to two main subpopulations, with isolates from human clinical material and Asia being more predominant in cluster 1, and environmental and animals isolates and those from Europe in cluster 2. Our results are of critical concern, since realizing that the C. krusei resistance mechanisms and their genotyping are crucial for guiding specific therapy and for exploring the potential infection source.
Volume 66(2)
Pages e0185621
Published 2022-2-15
DOI 10.1128/AAC.01856-21
PMID 34871096
PMC PMC8846461
MeSH Animals Antifungal Agents / pharmacology Antifungal Agents / therapeutic use Azoles* / pharmacology Drug Resistance, Fungal / genetics Echinocandins* / pharmacology Genotype Microbial Sensitivity Tests Pichia Prevalence
IF 4.904
Pathogenic eukaryotic microorganisms Candida krusei IFM 5753, IFM 47972, IFM 51979, IFM 52777, IFM 53500