茴香菌素
卡斯波芬金
米卡芬金
光滑假丝酵母
生物
微生物学
突变
基因
无声突变
遗传学
两性霉素B
错义突变
白色念珠菌
抗真菌
作者
Saba Memon,Najia Karim Ghanchi,Urooj Zafar,Joveria Farooqi,Sadaf Zaka,Kauser Jabeen
出处
期刊:Mycoses
[Wiley]
日期:2022-09-21
卷期号:66 (1): 52-58
摘要
The gradual increase in caspofungin usage in Pakistan raises a concern of emergence of echinocandin resistance in local Candida glabrata strains. We sequenced and determined mutations in fks1 and fks2 genes in invasive Candida glabrata strains from Pakistan.Thirty-six invasive C. glabrata strains were selected with median (min-max) minimum inhibitory concentrations (MICs) of 0.06 (0.015-0.25) mg/L for caspofungin, 0.015 (0.008-0.06) mg/L for micafungin and 0.06 (0.015-0.12) mg/L for anidulafungin. fks1 and fks2 gene fragments were sequenced using Sanger methodology. Sequences were analysed with MEGA-6 software to identify specific single-nucleotide polymorphisms (SNP) against wild-type sequences of C. glabrata.In fks1 gene, non-synonymous mutation D632H was observed in one isolate with caspofungin MIC of 0.25 mg/L. Synonymous mutation at position A742 was observed in 26/36 (72%) of the isolates. 34/36 (94.5%) isolates analysed for fks2 gene were observed as wild type. A novel non-synonymous mutation at I661T was observed in fks2 gene in one isolate with caspofungin MIC of 0.12 mg/L and anidulafungin and micafungin MIC of 0.06 and 0.015 mg/L, respectively. Novel fks2 synonymous mutations at position T647, K652 and I706 were observed in 16/36 (44%), 25/36 (69%) and 23/36 (63%) isolates, respectively.Low frequencies of both non-synonymous and synonymous polymorphisms were observed in invasive C. glabrata strains. Since S663P in fks2 gene is associated with caspofungin resistance, a novel mutation at 661 codon identified in our study needs correlation with treatment outcome data and mandates periodic genomic surveillance.
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