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 of aspergillus diseases. There are currently two presumed routes for medical triazole-resistance selection: (i) through selection pressure of medical triazoles when treating patients and (ii) through selection pressure from non-medical 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 one of five different SI fungicides to select for resistance. In our evolved lines we found widespread 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（medical triazoles）的耐药性，已成为曲霉病（aspergillus diseases）高危患者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筛选的途径：其一为患者治疗过程中，医用三唑类药物施加的选择压力；其二为环境中使用的非医用麦角固醇生物合成抑制型（sterol-biosynthesis-inhibiting，SI）三唑类杀菌剂所带来的选择压力。既往研究表明，此类SI杀菌剂可诱导对医用三唑类药物的交叉耐药性。为评估环境中医用三唑类耐药性的潜在选择风险，我们针对前期实验获得的烟曲霉耐药谱系，评估了其对三种医用三唑类药物的交叉耐药性：前期实验通过五种不同SI杀菌剂之一施加选择压力，采用实验进化（experimental evolution）方法筛选获得耐药菌株。本研究在上述进化获得的耐药谱系中，发现了广泛存在的交叉耐药现象，提示医用三唑类药物的耐药性可在SI杀菌剂的选择压力下快速产生。所有耐药谱系均表现出与SI杀菌剂及医用三唑类药物高度相似的进化动力学特征，这表明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，其中部分突变位于已知的靶标基因（target genes）中。