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模型与病原体:细菌中的 FtsZ 有多保守?

Models versus pathogens: how conserved is the FtsZ in bacteria?

机构信息

Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India.

National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Punjab 160062, India.

出版信息

Biosci Rep. 2023 Feb 27;43(2). doi: 10.1042/BSR20221664.

Abstract

Combating anti-microbial resistance by developing alternative strategies is the need of the hour. Cell division, particularly FtsZ, is being extensively studied for its potential as an alternative target for anti-bacterial therapy. Bacillus subtilis and Escherichia coli are the two well-studied models for research on FtsZ, the leader protein of the cell division machinery. As representatives of gram-positive and gram-negative bacteria, respectively, these organisms have provided an extensive outlook into the process of cell division in rod-shaped bacteria. However, research on other shapes of bacteria, like cocci and ovococci, lags behind that of model rods. Even though most regions of FtsZ show sequence and structural conservation throughout bacteria, the differences in FtsZ functioning and interacting partners establish several different modes of division in different bacteria. In this review, we compare the features of FtsZ and cell division in the model rods B. subtilis and E. coli and the four pathogens: Staphylococcus aureus, Streptococcus pneumoniae, Mycobacterium tuberculosis, and Pseudomonas aeruginosa. Reviewing several recent articles on these pathogenic bacteria, we have highlighted the functioning of FtsZ, the unique roles of FtsZ-associated proteins, and the cell division processes in them. Further, we provide a detailed look at the anti-FtsZ compounds discovered and their target bacteria, emphasizing the need for elucidation of the anti-FtsZ mechanism of action in different bacteria. Current challenges and opportunities in the ongoing journey of identifying potent anti-FtsZ drugs have also been described.

摘要

通过开发替代策略来对抗抗微生物耐药性是当下的需求。细胞分裂,特别是 FtsZ,因其作为抗菌治疗替代靶标的潜力而受到广泛研究。枯草芽孢杆菌和大肠杆菌是研究 FtsZ 的两个经过充分研究的模型,FtsZ 是细胞分裂机制的主导蛋白。作为革兰氏阳性菌和革兰氏阴性菌的代表,这些生物体为杆状细菌的细胞分裂过程提供了广泛的视角。然而,对于其他形状的细菌(如球菌和卵形球菌)的研究落后于模型棒的研究。尽管 FtsZ 的大多数区域在整个细菌中显示出序列和结构的保守性,但 FtsZ 功能和相互作用伙伴的差异在不同的细菌中建立了几种不同的分裂模式。在这篇综述中,我们比较了模型棒状菌枯草芽孢杆菌和大肠杆菌以及四种病原体(金黄色葡萄球菌、肺炎链球菌、结核分枝杆菌和铜绿假单胞菌)中 FtsZ 和细胞分裂的特征。通过回顾关于这些致病菌的几篇最新文章,我们强调了 FtsZ 的功能、FtsZ 相关蛋白的独特作用以及它们的细胞分裂过程。此外,我们详细介绍了已发现的抗 FtsZ 化合物及其靶细菌,强调了阐明不同细菌中抗 FtsZ 作用机制的必要性。还描述了在确定有效抗 FtsZ 药物的持续研究中当前面临的挑战和机遇。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7430/9939409/bc8412ff63c0/bsr-43-bsr20221664-g1.jpg

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