Resendiz-Sharpe Agustin, Hokken Margriet W J, Mercier Toine, Merckx Rita, Verhagen Kamiel, Dewitte Lisa, Melchers Willem J G, Verweij Paul E, Maertens Johan, Lagrou Katrien
Department of Microbiology, Immunology and Transplantation, Laboratory of Clinical Bacteriology and Mycology, KU Leuven, 3000 Leuven, Belgium.
Department of Medical Microbiology, Radboud University Nijmegen Medical Center, Radboud Institute for Molecular Life Sciences, 6525 Nijmegen, The Netherlands.
J Fungi (Basel). 2020 Oct 16;6(4):227. doi: 10.3390/jof6040227.
Recently, mutations in the -encoding gene (), a gene involved in ergosterol production, were associated with triazole-resistance in . In this study, we determined the prevalence and characteristics of mutations in a collection of clinical triazole-resistant isolates collected during 2001-2019 from two international mycology reference centers: the Belgian National Reference Center for Mycosis and the Center of Expertise in Mycology Radboudumc/CWZ. Clinical isolates with and without gene mutations and randomly selected wild-type (WT) controls were included. Isolates were characterized by in vitro susceptibility testing, and sequencing, and short tandem repeat typing. Available clinical records were analyzed for previous triazole exposure. In 23 isolates (24%) of the 95 triazole-resistant isolates, gene mutations were observed; including 5/23 (22%) isolates without gene mutations and 18/72 (25%) with mutations. Four previously described gene mutations (E105K, G307R/D, G466V, and S541G) and two novel mutations (W273S and L304P) were found; 4/23 (17%) in the sterol-sensing-domain region. No triazole-antifungal exposure was reported in 75% (9/12) of patients harboring an isolate with gene mutations. Three of 39 WT isolates (8%) contained a gene mutation; E105K (2-isolates) and S541G. gene mutations were predominantly found in with mutations with voriconazole MICs ≥ 8 mg/L.
最近，参与麦角甾醇生成的编码基因（）中的突变与对三唑类药物的耐药性有关。在本研究中，我们确定了2001年至2019年期间从两个国际真菌学参考中心（比利时国家真菌病参考中心和拉德堡德大学医学中心/ CWZ真菌学专业知识中心）收集的临床三唑类耐药分离株中基因突变的发生率和特征。纳入了有和没有基因突变的临床分离株以及随机选择的野生型（WT）对照。通过体外药敏试验、测序和短串联重复序列分型对分离株进行特征分析。分析可用的临床记录以了解先前的三唑类药物暴露情况。在95株三唑类耐药分离株中的23株（24%）中观察到基因突变；其中5/23（22%）株没有基因突变，18/72（25%）株有基因突变。发现了四个先前描述的基因突变（E105K、G307R/D、G466V和S541G）以及两个新突变（W273S和L304P）；4/23（17%）位于甾醇感应结构域区域。携带具有基因突变分离株的患者中，75%（9/12）未报告有三唑类抗真菌药物暴露史。39株野生型分离株中有3株（8%）含有基因突变；E105K（2株）和S541G。基因突变主要在伏立康唑最低抑菌浓度≥8 mg/L的有基因突变的菌株中发现。
