Genetically related micafungin-resistant Candida parapsilosis blood isolates harbouring novel mutation R658G in hotspot 1 of Fks1p: a new challenge?
| Autor: | Süleyha Hilmioğlu-Polat, Ülküm Zafer Dokumcu, Dilek Yeşim Metin, Weihua Pan, Farnaz Daneshnia, Amir Arastehfar, Macit Ilkit, Ferry Hagen, Melike Yaşar, Furkan Polat, David S. Perlin, Cornelia Lass-Flörl, Teun Boekhout |
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| Přispěvatelé: | Westerdijk Fungal Biodiversity Institute, Westerdijk Fungal Biodiversity Institute - Medical Mycology, Westerdijk Fungal Biodiversity Institute - Yeast Research, Evolutionary and Population Biology (IBED, FNWI) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Microbiology (medical)
Antifungal Agents Candida parapsilosis Echinocandin Microbial Sensitivity Tests Microbiology chemistry.chemical_compound Echinocandins Drug Resistance Fungal Amphotericin B Genotype medicine polycyclic compounds Humans Pharmacology (medical) Typing Child Pharmacology biology Micafungin Erg11 Gene biology.organism_classification bacterial infections and mycoses Glabrata Infectious Diseases chemistry Mutation Anidulafungin Caspofungin medicine.drug |
| Zdroj: | Journal of Antimicrobial Chemotherapy. Oxford University Press Journal of Antimicrobial Chemotherapy, 76(2). Oxford University Press |
| ISSN: | 0305-7453 |
| Popis: | Background: Echinocandin resistance rarely occurs in clinical Candida parapsilosis isolates and the underlying mechanism is unknown. Objectives: To determine the prevalence of echinocandin resistance and the underlying mechanism for a Large collection of C. parapsilosis blood isolates and to determine whether the echinocandin-resistant isolates were clonally related. Methods: C. parapsilosis blood isolates (n = 213) were subjected to antifungal susceptibility testing (CLSI M27), for micafungin, anidulafungin, amphotericin B and, if appropriate, caspofungin. Hotspot (HS) 1 and HS2 of FKS1 were sequenced for all isolates (n = 213) and microsatellite typing was performed for echinocandin-resistant isolates. Results: ALL isolates were susceptible to amphotericin B and two isolates were intermediate to anidulafungin (MIC-4 mg/L), while micafungin resistance was noted in four isolates (MIC >8 mg/L); three of which were also fluconazole resistant and therefore were MDR. Interestingly, micafungin-resistant isolates, but not those intermediate to anidulafungin, carried novel mutation R658G in HS1 of Fks1p; three of which also harboured Y132F+K143R in Erg11. The first isolate (MICR1) was recovered in November 2017 from a patient admitted to paediatric gastroenterology who showed therapeutic failure under caspofungin treatment. MICR2-MICR4 were collected during 2018-19 and were recovered from three echinocandin-naive paediatric-surgery patients; the isolates shared the same genotype. Conclusions: Herein, for the first time (to the best of our knowledge), we identified micafungin-resistant C. parapsilosis blood isolates harbouring a novel mutation in HS1 of FKS1, which was Likely attributable to in vitro micafungin resistance and in vivo caspofungin therapeutic failure. The acquisition of micafungin-resistant C. parapsilosis isolates in echinocandin-naive patients Likely implicates clonal expansion, as supported by the close genetic relatedness of MICR2-MICR4. Major National R&D Projects of the National Health Department [2018ZX10101003]; National Natural Science Foundation of China [31770161]; Shanghai Science and Technology Committee [17DZ2272900, 14495800500]; Shanghai Municipal Commission of Health and Family Planning [2017ZZ01024-001]; Shanghai Sailing Program [19YF1448000]; Chinese Academy of Engineering [2019-XY-33] This work was supported by the Major National R&D Projects of the National Health Department (2018ZX10101003), the National Natural Science Foundation of China (31770161), the Shanghai Science and Technology Committee (17DZ2272900 and 14495800500), the Shanghai Municipal Commission of Health and Family Planning (2017ZZ01024-001), the Shanghai Sailing Program (19YF1448000) and the Chinese Academy of Engineering (2019-XY-33). |
| Databáze: | OpenAIRE |
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