Hao Haihong, Cheng Guyue, Dai Menghong, Wu Qinghua, Yuan Zonghui
National Reference Laboratory of Veterinary Drug Residues and MOA Key Laboratory for the Detection of Veterinary Drug Residues in Foods, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
Mol Biosyst. 2012 Nov;8(11):2828-38. doi: 10.1039/c2mb25188d. Epub 2012 Aug 16.
Methicillin resistant Staphylococcus aureus (MRSA), widely known as a type of new superbug, has aroused world-wide concern. Cell wall biosynthesis pathway is an old but good target for the development of antibacterial agents. Peptidoglycan and wall teichoic acids (WTAs) biosynthesis are two main processes of the cell wall biosynthesis pathway (CWBP). Other than penicillin-binding proteins (PBPs), some key factors (Mur enzymes, lipid I or II precursor, etc.) in CWBP are becoming attractive molecule targets for the discovery of anti-MRSA compounds. A number of new compounds, with higher affinity for PBPs or with inhibitory activity on such molecule targets in CWBP of MRSA, have been in the pipeline recently. This review concludes recent research achievements and provides a complete picture of CWBP of MRSA, including the peptidoglycan and wall teichoic acids synthesis pathway. The potential inhibitors targeting on CWBP are subsequently presented to improve development of novel therapeutic strategies for MRSA.
耐甲氧西林金黄色葡萄球菌(MRSA),广为人知的一种新型超级细菌,已引起全球关注。细胞壁生物合成途径是开发抗菌剂的一个古老但很好的靶点。肽聚糖和壁磷壁酸(WTAs)生物合成是细胞壁生物合成途径(CWBP)的两个主要过程。除青霉素结合蛋白(PBPs)外,CWBP中的一些关键因子(Mur酶、脂质I或II前体等)正成为发现抗MRSA化合物的有吸引力的分子靶点。最近有许多对PBPs具有更高亲和力或对MRSA的CWBP中的此类分子靶点具有抑制活性的新化合物正在研发中。本综述总结了近期的研究成果,并提供了MRSA的CWBP的全貌,包括肽聚糖和壁磷壁酸合成途径。随后介绍了针对CWBP的潜在抑制剂,以促进MRSA新型治疗策略的开发。