Department of Infectious Diseases, Huashan Hospital and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
Institute of Clinical Medicine and Dermatology Department, Jiangxi Provincial People's Hospital Affiliated to Nanchang Univercity, Nanchang, China.
Virulence. 2021 Dec;12(1):1388-1399. doi: 10.1080/21505594.2021.1928410.
The fungal pathogen has emerged as a new threat to human health. We previously reported the first isolate of (BJCA001) in China, which belongs to the South Asian clade (I) and was susceptible to all antifungals tested. In this study, we report the isolation of a drug-resistant strain (BJCA002) from the same city (Beijing). Strain BJCA002 belongs to the South African clade (III) and is resistant to fluconazole and amphotericin B based on the tentative MIC breakpoints. Taking advantage of the two isolates with distinct antifungal susceptibility and genetic origins, we performed a biological and genomic comparative study. Besides antifungal susceptibility, strains BJCA001 and BJCA002 showed differences in multiple aspects including morphologies, expression of virulence factors, virulence, mating type, and genomic sequence and organization. Notably, strain BJCA002 was less virulent than BJCA001 in both the and mouse systemic infection models. Genomic analysis demonstrated that strain BJCA002 but not BJCA001 had multiple mutations in drug resistance-associated genes, including a hot-spot mutation of (VF125AL, namely V125A and F126L) and some missense mutations in , and . Notably, strain BJCA001 carried 64 copies of the Zorro3 retrotransposon, whereas BJCA002 had only 3 copies in the genome. Taken together, our findings not only reveal the genetic and phenotypic diversities of the two isolates from Beijing, China, but also shed new light on the genetic basis of the antifungal resistance and virulence of
真菌病原体已成为人类健康的新威胁。我们之前曾报道过在中国的第一个 （BJCA001）分离株，它属于南亚分支（I），对所有测试的抗真菌药物均敏感。在这项研究中，我们报告了来自同一城市（北京）的耐药 株（BJCA002）的分离。菌株 BJCA002 属于南非分支（III），基于暂定 MIC 断点，对氟康唑和两性霉素 B 耐药。利用具有明显抗真菌敏感性和遗传起源的两个分离株，我们进行了生物学和基因组比较研究。除了抗真菌敏感性外，菌株 BJCA001 和 BJCA002 在形态、毒力因子表达、毒力、交配型以及基因组序列和组织等多个方面表现出差异。值得注意的是，菌株 BJCA002 在 和小鼠系统性感染模型中的毒力均低于 BJCA001。基因组分析表明，菌株 BJCA002 而不是 BJCA001 在耐药相关基因中存在多个突变，包括 （VF125AL，即 V125A 和 F126L）热点突变和 、 中的一些错义突变。值得注意的是，菌株 BJCA001 携带 64 个 Zorro3 反转录转座子拷贝，而 BJCA002 基因组中只有 3 个拷贝。总之，我们的研究结果不仅揭示了来自中国北京的两个分离株的遗传和表型多样性，还为抗真菌耐药性和毒力的遗传基础提供了新的见解。
