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使用秀丽隐杆线虫体内模型寻找新型抗菌剂的平台

Platforms for the Search for New Antimicrobial Agents Using In Vivo C. elegans Models.

作者信息

Kalganova A I, Eliseev I E, Smirnov I V, Terekhov S S

机构信息

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, 117997 Russian Federation.

Department of Chemistry, Lomonosov Moscow State University, Moscow, 119991 Russian Federation.

出版信息

Acta Naturae. 2024 Oct-Dec;16(4):15-26. doi: 10.32607/actanaturae.27348.

Abstract

Despite the achievements brought about by high-throughput screening technologies, there is still a lack of effective platforms to be used to search for new antimicrobial drugs. The antimicrobial activity of compounds continues, for the most part, to be assessed mainly using pathogen cultures, a situation which does not make easy a detailed investigation of the molecular mechanisms underlying host-pathogen interactions. testing of promising compounds using chordate models is labor-intensive and expensive and, therefore, is used in preclinical studies of selected drug candidates but not in primary screening. This approach does not facilitate the selection of compounds with low organ toxicity and is not suitable for the identification of therapeutic compounds that affect virulence factors. The use of microscopic nematode to model human infections is a promising approach that enables one to investigate the host-pathogen interaction and identify anti-infective compounds with new mechanisms of action.

摘要

尽管高通量筛选技术带来了诸多成果,但仍缺乏用于寻找新型抗菌药物的有效平台。化合物的抗菌活性在很大程度上仍主要通过病原体培养来评估,这种情况不利于对宿主 - 病原体相互作用的分子机制进行详细研究。使用脊索动物模型对有前景的化合物进行测试既耗费人力又成本高昂,因此仅用于选定候选药物的临床前研究,而不用于初步筛选。这种方法不利于选择低器官毒性的化合物,也不适合鉴定影响毒力因子的治疗性化合物。利用微小线虫模拟人类感染是一种很有前景的方法,能够研究宿主 - 病原体相互作用并鉴定具有新作用机制的抗感染化合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0b6/11771841/f8b4f25233e6/AN20758251-16-04-015-g001.jpg

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