Data from: Asexual sporulation facilitates adaptation: the emergence of azole resistance in Aspergillus fumigatus

Understanding the occurrence and spread of azole resistance in Aspergillus fumigatus is crucial for public health. It has been hypothesized that asexual sporulation, which is abundant in nature, is essential for phenotypic expression of azole-resistance mutations in A. fumigatus facilitating subsequent spread through natural selection. Furthermore, the disease aspergilloma is associated with asexual sporulation within the lungs of patients and the emergence of azole resistance. This study assessed the evolutionary advantage of asexual sporulation by growing the fungus under pressure of one of five different azole fungicides over seven weeks and by comparing the rate of adaptation between scenarios of culturing with and without asexual sporulation. Results unequivocally show that asexual sporulation facilitates adaptation. This can be explained by the combination of more effective selection because of the transition from a multicellular to a unicellular stage, and by increased mutation supply due to the production of spores, which involves numerous mitotic divisions. Insights from this study are essential to unravel the resistance mechanisms of sporulating pathogens to chemical compounds and disease agents in general, and for designing strategies that prevent or overcome the emerging threat of azole resistance in particular.

阐明烟曲霉（Aspergillus fumigatus）唑类（azole）耐药性的发生与扩散机制，对公共卫生领域具有重要意义。已有假说提出，自然界中广泛存在的无性产孢（asexual sporulation）是烟曲霉唑类耐药突变表型表达的必要条件，并可通过自然选择推动耐药菌株的后续扩散。此外，肺曲菌球（aspergilloma）这一疾病与患者肺部的无性产孢过程以及唑类耐药性的出现紧密相关。本研究通过将烟曲霉置于五种唑类杀菌剂之一的选择压力下连续培养七周，并对比存在与缺失无性产孢两种培养条件下的适应速率，评估了无性产孢的进化优势。研究结果明确证实，无性产孢可促进耐药适应性的形成。该结论可通过双重机制得到阐释：其一，真菌从多细胞阶段向单细胞阶段的转变使得选择作用更为高效；其二，孢子生成过程涉及大量有丝分裂，进而提升了突变供给总量。本研究的发现，总体上可为阐明产孢病原物对化学制剂及各类致病因子的耐药机制提供支撑，尤其可为制定防控唑类耐药性这一新兴威胁的策略提供理论依据。