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细胞分裂蛋白 FtsZ:从结构和机制到抗生素靶标。

Cell division protein FtsZ: from structure and mechanism to antibiotic target.

机构信息

Department of Microbial Bioactive Compounds, Interfaculty Institute of Microbiology & Infection Medicine, University of Tübingen, Auf der Morgenstelle 28, Tübingen 72076, Germany.

German Center for Infection Research (DZIF), partner site Tübingen, Tübingen 72076, Germany.

出版信息

Future Microbiol. 2020 Jun;15:801-831. doi: 10.2217/fmb-2019-0348. Epub 2020 Jul 21.

Abstract

Antimicrobial resistance to virtually all clinically applied antibiotic classes severely limits the available options to treat bacterial infections. Hence, there is an urgent need to develop and evaluate new antibiotics and targets with resistance-breaking properties. Bacterial cell division has emerged as a new antibiotic target pathway to counteract multidrug-resistant pathogens. New approaches in antibiotic discovery and bacterial cell biology helped to identify compounds that either directly interact with the major cell division protein FtsZ, thereby perturbing the function and dynamics of the cell division machinery, or affect the structural integrity of FtsZ by inducing its degradation. The impressive antimicrobial activities and resistance-breaking properties of certain compounds validate the inhibition of bacterial cell division as a promising strategy for antibiotic intervention.

摘要

几乎所有临床应用抗生素类别的抗菌药物耐药性严重限制了治疗细菌感染的可用选择。因此,迫切需要开发和评估具有耐药性突破特性的新抗生素和靶标。细菌细胞分裂已成为一种新的抗生素靶标途径,以对抗多药耐药病原体。抗生素发现和细菌细胞生物学的新方法有助于确定那些直接与主要细胞分裂蛋白 FtsZ 相互作用的化合物,从而干扰细胞分裂机制的功能和动力学,或通过诱导其降解来影响 FtsZ 的结构完整性。某些化合物具有令人印象深刻的抗菌活性和耐药性突破特性,这验证了抑制细菌细胞分裂作为抗生素干预的一种有前途的策略。

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