Department of Clinical Laboratory, Aerospace Center Hospital, Beijing, 100049 China.
Zhejiang Key Laboratory of Digital Technology in Medical Diagnostics, Hangzhou, 310000 China.
Clinics (Sao Paulo). 2024 Sep 15;79:100497. doi: 10.1016/j.clinsp.2024.100497. eCollection 2024.
Candida auris is a globally disseminated invasive ascomycetous yeast, that imposes a substantial burden on healthcare systems. It has been documented to have spread to over 40 countries across six continents, necessitating in-depth comprehension through advanced techniques like Whole-Genome Sequencing.
This study entailed the isolation and Whole-Genome Sequencing of a fluconazole-resistant C. auris strain (CA01) obtained from a patient's blood in Beijing. Genome analysis was conducted to classify the strain, and molecular docking was performed to understand the impact of mutations on drug resistance.
Genome analysis revealed that CA01 belongs to the South Asia Clade (I) and shares the closest genetic relationship with previously reported strains BJCA001 and BJCA002. Notably, unlike BJCA001, CA01 exhibits significant resistance to fluconazole primarily due to the A395T mutation in the ERG11 gene. Molecular docking studies demonstrated that this mutation leads to geometric changes in the active site where fluconazole binds, resulting in decreased binding affinity. Additionally, the present findings have identified several core virulence genes in C. auris, such as RBF1.
The findings from this study expand the understanding of the genetic diversity and adaptive mechanisms of C. auris within the South Asia Clade (I). The observed fluconazole resistance driven by the ERG11 mutation A395T highlights the need for heightened awareness and adaptation in clinical treatment strategies in China. This study provides critical insights into drug resistance and virulence profiles at a genetic level, which could guide future therapeutic and management strategies for C. auris infections.
耳念珠菌是一种全球传播的侵袭性丝状酵母，对医疗保健系统造成了巨大负担。它已被记录传播到六大洲的 40 多个国家，需要通过全基因组测序等先进技术进行深入理解。
本研究涉及从北京一位患者血液中分离并进行全基因组测序的氟康唑耐药耳念珠菌（CA01）菌株。进行基因组分析以对该菌株进行分类，并进行分子对接以了解突变对耐药性的影响。
基因组分析表明，CA01 属于南亚进化枝（I），与先前报道的菌株 BJCA001 和 BJCA002 具有最密切的遗传关系。值得注意的是，与 BJCA001 不同，CA01 对氟康唑表现出显著的耐药性，主要是由于 ERG11 基因中的 A395T 突变。分子对接研究表明，该突变导致氟康唑结合的活性部位的几何形状发生变化，从而降低了结合亲和力。此外，本研究还发现了耳念珠菌中的几个核心毒力基因，如 RBF1。
本研究扩展了对南亚进化枝（I）内耳念珠菌遗传多样性和适应机制的理解。观察到的由 ERG11 基因突变 A395T 驱动的氟康唑耐药性突出表明，在中国需要提高对临床治疗策略的认识和适应。本研究从遗传水平上提供了有关耐药性和毒力谱的关键见解，这可能为未来的耳念珠菌感染治疗和管理策略提供指导。
