In Vitro Interactions of Antifungal Agents and Everolimus Against Aspergillus Species

被引:3
|
作者
Jiang, Huiping [1 ]
Xiong, Jianqun [2 ]
Tan, Lihua [3 ]
Jin, Ping [1 ]
Sun, Yi [3 ]
Yang, Lianjuan [4 ]
Tan, Jingwen [4 ]
机构
[1] Yangtze Univ, Jingzhou Cent Hosp, Clin Med Coll 2, Dept Crit Care Med, Jingzhou, Peoples R China
[2] Yangtze Univ, Jingzhou Cent Hosp, Clin Med Coll 2, Dept Pharm, Jingzhou, Peoples R China
[3] Yangtze Univ, Jingzhou Cent Hosp, Clin Med Coll 2, Candidate Branch,Natl Clin Res Ctr Skin & Immune D, Jingzhou, Peoples R China
[4] Tongji Univ, Shanghai Skin Dis Hosp, Dept Med Mycol, Sch Med, Shanghai, Peoples R China
基金
中国国家自然科学基金;
关键词
TOR pathway; TOR inhibitor; everolimus; azoles; Aspergillus; INVASIVE ASPERGILLOSIS; MTOR INHIBITOR; KINASE;
D O I
10.3389/fcimb.2022.936814
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 Aspergillus species derived from 35 clinical isolates in vitro. 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. In vivo experiments conducted in Galleria mellonella 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.
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页数:6
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