Recent progress of bacterial FtsZ inhibitors with a focus on peptides. (2nd August 2020)

• Record Type: Journal Article
• Authors: Han, Huihui; Wang, Zhenlong; Li, Ting; Teng, Da; Mao, Ruoyu; Hao, Ya; Yang, Na; Wang, Xiumin; Wang, Jianhua
• Is Part Of: FEBS journal. Volume 288:Number 4(2021)
• Page Start: 1091
• Page End: 1106
• Publication Date: 2020-08-02
• Subjects: antibacterial activity -- antibiotic resistance -- assembly -- cell division -- filament -- FtsZ -- GTPase activity -- inhibitor -- mechanism of action -- polymerization -- Z‐ring; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.15489
• Languages: English
• ISSNs: 1742-464X

Abstract

Abstract : In recent years, the rise of antibiotic resistance has become a primary health problem. With the emergence of bacterial resistance, the need to explore and develop novel antibacterial drugs has become increasingly urgent. Filamentous temperature‐sensitive mutant Z (FtsZ), a crucial cell division protein of bacteria, has become a vital antibacterial target. FtsZ is a filamentous GTPase; it is highly conserved in bacteria and shares less than 20% sequence identity with the eukaryotic cytoskeleton protein tubulin, indicating that FtsZ‐targeting antibacterial agents may have a low cytotoxicity toward eukaryotes. FtsZ can form a dynamic Z‐ring in the center of the cell resulting in cell division. Furthermore, disturbance in the assembly of FtsZ may affect cellular dynamics and bacterial cell survival, making it a fascinating target for drug development. This review focuses on the recent discovery of FtsZ inhibitors, including peptides, natural products, and other synthetic small molecules, as well as their mechanism of action, which could facilitate the discovery of novel FtsZ‐targeting clinical drugs in the future. Abstract : FtsZ, a crucial cell division protein, can form a dynamic Z‐ring in the cell center, causing the cell to divide. Disturbances in FtsZ assembly adversely affect cell division, highlighting FtsZ as a promising antibacterial target. FtsZ inhibitors, including peptides, natural products, and other synthetic small molecules, can inhibit GTPase activity and disturb FtsZ assembly and Z‐ring formation. This knowledge could facilitate the discovery of novel FtsZ‐targeting clinical drugs.