Data from: Evolution of cross-resistance to medical triazoles in Aspergillus fumigatus through selection pressure of environmental fungicides

Resistance to medical triazoles in Aspergillus fumigatus is an emerging problem for patients at risk for aspergillus diseases. There are currently two presumed routes for medical triazole-resistance selection, (1) through selection pressure of medical triazoles when treating patients, and (2) through selection pressure from environmental sterol biosynthesis inhibiting (SI) triazole fungicides which are used in the environment. Previous studies have suggested that SI fungicides can induce cross-resistance to medical triazoles. Therefore, to assess the potential of selection of resistance to medical triazoles in the environment, we assessed cross-resistance to three medical triazoles in lineages of A. fumigatus from previous work where we applied an experimental evolution approach with of one of five different SI fungicides to select for resistance. In our evolved lines we found wide-spread cross-resistance indicating that resistance to medical triazoles rapidly arises through selection pressure of SI fungicides. All evolved lineages showed similar evolutionary dynamics to SI fungicides and medical triazoles, which suggests that the mutations inducing resistance to both SI fungicides and medical triazoles are likely to be the same. Whole-genome sequencing revealed that a variety of mutations were putatively involved in the resistance mechanism, some of which are in known target genes.烟曲霉（Aspergillus fumigatus）对医用三唑类药物的耐药性，已成为曲霉病高危患者群体面临的新兴临床难题。目前推测存在两条介导医用三唑类耐药性产生的途径：其一为患者临床治疗过程中，医用三唑类药物施加的选择压力；其二为环境中广泛使用的固醇生物合成抑制（SI）类三唑杀菌剂带来的选择压力。既往研究已证实，SI类杀菌剂可诱导烟曲霉对医用三唑类药物产生交叉耐药性（cross-resistance）。为评估环境因素下医用三唑类耐药性的潜在选择潜力，我们针对前期实验进化（experimental evolution）研究获得的烟曲霉谱系，开展了针对3种医用三唑类药物的交叉耐药性检测——该前期研究通过施加5种不同SI类杀菌剂之一的选择压力，采用实验进化策略筛选获得耐药菌株。本研究在构建的进化菌株谱系中，观察到广泛分布的交叉耐药性现象，表明医用三唑类药物的耐药性可通过SI类杀菌剂的选择压力快速演化形成。所有进化谱系均展现出与SI类杀菌剂及医用三唑类药物相似的进化动力学特征，这提示介导两类药剂耐药性的突变大概率为同一类突变。全基因组测序（whole-genome sequencing）结果显示，多种突变可能参与了耐药机制的形成，其中部分突变位于已知的药物靶标基因中。