Department of Critical Care Medicine, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, China.
Department of Pharmacy, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, China.
Front Cell Infect Microbiol. 2022 Jul 5;12:936814. doi: 10.3389/fcimb.2022.936814. eCollection 2022.
Multiple cellular activities, including protein and lipid synthesis, ribosome biogenesis, and metabolic processes, are regulated by the target of rapamycin (TOR) pathway. Recent research suggests that the TOR might play an important role in various physiological functions of pathogenic fungi, such as nutrient sensing, stress response, and cell cycle progression. Given their robust immunosuppressant and antitumor activities, TOR inhibitors are widely used in clinical settings. In the present study, a microdilution checkerboard-based approach was employed to assess the interactions between the oral mammalian target of rapamycin (mTOR) inhibitor everolimus (EVL) and antifungal agents in the treatment of species derived from 35 clinical isolates The results revealed that EVL exhibited promising inhibitory synergy with itraconazole (ITC), posaconazole (POS), and amphotericin B (AMB) for 85.7%, 74.2%, and 71.4%, respectively. In contrast, EVL exhibited minimal synergistic inhibitory activity (14.3%) when applied in combination with voriconazole (VRC). Antagonistic interactions were not observed. experiments conducted in revealed that EVL in combination with antifungal agents improved the larva survival rates in the ITC, VRC, POS, and AMB groups by 18.3%, 13.3%, 26.7%, and 13.3%, respectively. These data suggest that the combination treatment with antifungal agents and antifungal agents holds promise as a means of alleviating clinical aspergillosis.
雷帕霉素（TOR）途径调控多种细胞活动，包括蛋白质和脂质合成、核糖体生物发生和代谢过程。最近的研究表明，TOR 可能在致病真菌的各种生理功能中发挥重要作用，如营养感应、应激反应和细胞周期进程。鉴于 TOR 抑制剂具有强大的免疫抑制和抗肿瘤活性，它们被广泛应用于临床环境中。在本研究中，采用微量稀释棋盘法评估了口服哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂依维莫司（EVL）与抗真菌药物联合治疗 35 株临床分离株来源的 种的相互作用。结果表明，EVL 与伊曲康唑（ITC）、泊沙康唑（POS）和两性霉素 B（AMB）联合使用时表现出有前途的抑制协同作用，分别为 85.7%、74.2%和 71.4%。相比之下，EVL 与伏立康唑（VRC）联合使用时表现出最小的协同抑制活性（14.3%）。未观察到拮抗相互作用。在 中进行的实验表明，EVL 与抗真菌药物联合使用可分别将 ITC、VRC、POS 和 AMB 组中的幼虫存活率提高 18.3%、13.3%、26.7%和 13.3%。这些数据表明，联合使用抗真菌药物和抗真菌药物治疗可能是缓解临床侵袭性曲霉病的一种方法。
