Zhu Rui, Yu Xia, Zhang Tingting, Kong Yaoyao, Wang Fen, Jia Junnan, Xue Yi, Huang Hairong
National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory on Drug-Resistant Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing, China.
Front Microbiol. 2022 Jul 26;13:926361. doi: 10.3389/fmicb.2022.926361. eCollection 2022.
The high level of inherent drug resistance of makes the infection caused by it very difficult to be treated. The objective of this study was to evaluate the potential of nosiheptide (NOS) as a new drug candidate for treating infections. The microplate AlamarBlue assay was performed to determine the minimum inhibitory concentrations (MICs) of NOS for 28 reference strains of rapidly growing mycobacteria (RGM) and 77 clinical isolates of . Time-kill kinetic and post-antibiotic effect (PAE) of NOS against was evaluated. Its bactericidal activity against in macrophages was determined by an intracellular colony numerating assay. NOS manifested good activity against the reference strains of RGM and clinical isolates . The MICs of NOS against clinical isolates ranged from 0.0078 to 1 μg/ml, and the MIC and MIC were 0.125 μg/ml and 0.25 μg/ml, respectively. The pattern of growth and kill by NOS against was moderate with apparent concentration-dependent characteristics, and the PAE value of NOS was found to be ~6 h. Furthermore, NOS had low cell toxicity against the THP-1 cell line after 48 h of exposure (IC = 106.9 μM). At 4 μg/ml, NOS exhibited high intracellular bactericidal activity against reference strains with an inhibitory rate of 66.52% ± 1.51%, comparable with that of clarithromycin at 2 μg/ml. NOS showed suitable inhibitory activities against and in macrophages and could be a potential drug candidate to treat infection.
[病原体名称]的高水平固有耐药性使得由其引起的感染极难治疗。本研究的目的是评估诺西肽（NOS）作为治疗[病原体名称]感染的新药候选物的潜力。采用微孔板AlamarBlue法测定了NOS对28株快速生长分枝杆菌（RGM）参考菌株和77株[病原体名称]临床分离株的最低抑菌浓度（MIC）。评估了NOS对[病原体名称]的时间杀菌动力学和抗生素后效应（PAE）。通过细胞内菌落计数法测定了其对巨噬细胞内[病原体名称]的杀菌活性。NOS对RGM参考菌株和[病原体名称]临床分离株表现出良好的活性。NOS对[病原体名称]临床分离株的MIC范围为0.0078至1μg/ml．对[具体菌株1]和[具体菌株2]的MIC分别为0.125μg/ml和0.25μg/ml。NOS对[病原体名称]的生长和杀灭模式适中，具有明显的浓度依赖性特征，且发现NOS的PAE值约为6小时。此外，暴露48小时后，NOS对THP-1细胞系的细胞毒性较低（IC = 106.9μM）。在4μg/ml时，NOS对[病原体名称]参考菌株表现出高细胞内杀菌活性，抑制率为66.52%±1.51%，与2μg/ml的克拉霉素相当。NOS对巨噬细胞内的[病原体名称]表现出合适的抑制活性，可能是治疗[病原体名称]感染的潜在药物候选物。
