Chen Meng-Meng, Shi Guo-Hui, Dai Yi, Fang Wen-Xia, Wu Qi
State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
University of Chinese Academy of Sciences, Beijing, China.
Front Genet. 2023 May 9;14:1133593. doi: 10.3389/fgene.2023.1133593. eCollection 2023.
is one of the most common pathogenic fungi, which results in high morbidity and mortality in immunocompromised patients. Amphotericin B (AMB) is used as the core drug for the treatment of triazole-resistant . Following the usage of amphotericin B drugs, the number of amphotericin B-resistant isolates showed an increasing trend over the years, but the mechanism and mutations associated with amphotericin B sensitivity are not fully understood. In this study, we performed a -mer-based genome-wide association study (GWAS) in 98 isolates from public databases. Associations identified with -mers not only recapitulate those with SNPs but also discover new associations with insertion/deletion (indel). Compared to SNP sites, the indel showed a stronger association with amphotericin B resistance, and a significant correlated indel is present in the exon region of , encoding a fumarylacetoacetate hydrolase (FAH) family protein. Enrichment analysis revealed sphingolipid synthesis and transmembrane transport may be related to the resistance of to amphotericin B. The expansion of variant types detected by the -mer method increases opportunities to identify and exploit complex genetic variants that drive amphotericin B resistance, and these candidate variants help accelerate the selection of prospective gene markers for amphotericin B resistance screening in .
是最常见的致病真菌之一，在免疫功能低下的患者中导致高发病率和死亡率。两性霉素B（AMB）被用作治疗三唑耐药菌的核心药物。随着两性霉素B药物的使用，多年来对两性霉素B耐药的分离株数量呈上升趋势，但与两性霉素B敏感性相关的机制和突变尚未完全了解。在本研究中，我们对来自公共数据库的98株分离株进行了基于-mer的全基因组关联研究（GWAS）。用-mer鉴定的关联不仅概括了与单核苷酸多态性（SNP）相关的关联，还发现了与插入/缺失（indel）的新关联。与SNP位点相比，indel与两性霉素B耐药性的关联更强，并且在编码富马酰乙酰乙酸水解酶（FAH）家族蛋白的基因的外显子区域存在一个显著相关的indel。富集分析表明鞘脂合成和跨膜转运可能与该菌对两性霉素B的耐药性有关。通过-mer方法检测到的变异类型的扩展增加了识别和利用驱动两性霉素B耐药性的复杂遗传变异的机会，这些候选变异有助于加速在该菌中筛选两性霉素B耐药性的前瞻性基因标记的选择。
