PDF(Pubmed)
Abstract：
Novel antifungal drugs are urgently needed to treat candidiasis caused by the emerging fungal multidrug-resistant pathogen Candida auris. In this study, the most cost-effective drug repurposing technology was adopted to identify an appropriate option among the 1615 clinically approved drugs with anti-C. auris activity. High-throughput virtual screening of 1,3-beta-glucanosyltransferase inhibitors was conducted, followed by an analysis of the stability of 1,3-beta-glucanosyltransferase drug complexes and 1,3-beta-glucanosyltransferase-dutasteride metabolite interactions and the confirmation of their activity in biofilm formation and planktonic growth. The analysis identified dutasteride, a drug with no prior antifungal indications, as a potential medication for anti-auris activity in seven clinical C. auris isolates from Saudi Arabian patients. Dutasteride was effective at inhibiting biofilm formation by C. auris while also causing a significant reduction in planktonic growth. Dutasteride treatment resulted in disruption of the cell membrane, the lysis of cells, and crushed surfaces on C. auris, and significant (p-value = 0.0057) shrinkage in the length of C. auris was noted at 100,000×. In conclusion, the use of repurposed dutasteride with anti-C. auris potential can enable rapid recovery in patients with difficult-to-treat candidiasis caused by C. auris and reduce the transmission of nosocomial infection.
摘要：
迫切需要新型抗真菌药物来治疗由新兴的真菌多药耐药病原体耳念珠菌引起的念珠菌病。在这项研究中,采用最具成本效益的药物再利用技术，在1615种临床批准的抗C药物中确定合适的选择。极光活动。进行了1,3-β-葡萄糖基转移酶抑制剂的高通量虚拟筛选，然后分析1,3-β-葡糖基转移酶药物复合物和1,3-β-葡糖基转移酶-度他雄胺代谢物相互作用的稳定性，并确认它们在生物膜形成和浮游生长中的活性。分析确定了度他雄胺，一种没有抗真菌适应症的药物，作为来自沙特阿拉伯患者的7种临床C.auris分离株的抗耳活性的潜在药物。度他雄胺可有效抑制C.auris的生物膜形成，同时还导致浮游生长的显着减少。度他雄胺治疗导致细胞膜破裂，细胞的裂解，和C.auris上压碎的表面，并且注意到C.auris长度的显着收缩（p值=0.0057）为100,000×。总之,使用抗C.耳电位可以使难以治疗的念珠菌病患者迅速康复，并减少医院感染的传播。
