Zhou Jingxuan, Cai Yi, Liu Ying, An Haoyue, Deng Kaihong, Ashraf Muhammad Awais, Zou Lili, Wang Jun
The People's Hospital of China Three Gorges University, Yichang, Hubei, China.
Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Sciences, China Three Gorges University, Yichang, Hubei, China.
Front Microbiol. 2022 Sep 23;13:952633. doi: 10.3389/fmicb.2022.952633. eCollection 2022.
Since the advent of penicillin, humans have known about and explored the phenomenon of bacterial inhibition antibiotics. However, with changes in the global environment and the abuse of antibiotics, resistance mechanisms have been selected in bacteria, presenting huge threats and challenges to the global medical and health system. Thus, the study and development of new antimicrobials is of unprecedented urgency and difficulty. Bacteria surround themselves with a cell wall to maintain cell rigidity and protect against environmental insults. Humans have taken advantage of antibiotics to target the bacterial cell wall, yielding some of the most widely used antibiotics to date. The cell wall is essential for bacterial growth and virulence but is absent from humans, remaining a high-priority target for antibiotic screening throughout the antibiotic era. Here, we review the extensively studied targets, i.e., MurA, MurB, MurC, MurD, MurE, MurF, Alr, Ddl, MurI, MurG, lipid A, and BamA in the cell wall, starting from the very beginning to the latest developments to elucidate antimicrobial screening. Furthermore, recent advances, including MraY and MsbA in peptidoglycan and lipopolysaccharide, and tagO, LtaS, LspA, Lgt, Lnt, Tol-Pal, MntC, and OspA in teichoic acid and lipoprotein, have also been profoundly discussed. The review further highlights that the application of new methods such as macromolecular labeling, compound libraries construction, and structure-based drug design will inspire researchers to screen ideal antibiotics.
自青霉素问世以来，人类就已了解并探索了抗生素抑制细菌的现象。然而，随着全球环境的变化以及抗生素的滥用，细菌中已筛选出耐药机制，这给全球医疗卫生系统带来了巨大威胁与挑战。因此，新型抗菌药物的研究与开发具有前所未有的紧迫性和难度。细菌通过细胞壁包围自身，以维持细胞的刚性并抵御外界侵害。人类利用抗生素作用于细菌细胞壁，从而产生了一些迄今为止应用最为广泛的抗生素。细胞壁对于细菌的生长和致病性至关重要，但人体细胞没有细胞壁，在整个抗生素时代，细胞壁仍然是抗生素筛选的重点靶点。在此，我们综述了细胞壁中经过广泛研究的靶点，即MurA、MurB、MurC、MurD、MurE、MurF、Alr、Ddl、MurI、MurG、脂多糖A和BamA，从最初的研究到最新进展，以阐明抗菌药物筛选情况。此外，还深入讨论了近期的进展，包括肽聚糖和脂多糖中的MraY和MsbA，以及磷壁酸和脂蛋白中的tagO、LtaS、LspA、Lgt、Lnt、Tol-Pal、MntC和OspA。该综述进一步强调，大分子标记、化合物库构建和基于结构的药物设计等新方法的应用将激励研究人员筛选出理想的抗生素。
