Yang Junshu, Brown Christopher, Noland Wayland, Johnson Timothy J, Ji Yinduo
Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN 55108, USA.
Department of Chemistry, University of Minnesota, Minneapolis, MN 55454, USA.
Antibiotics (Basel). 2022 Nov 4;11(11):1550. doi: 10.3390/antibiotics11111550.
The discovery of new classes of antibiotics is slow, and it is being greatly outpaced by the development of bacterial resistance. This disparity places us in an increasingly vulnerable position because we are running out of safe and effective therapeutic options to treat antibiotic-resistant infections. This is exemplified by the emergence and persistence of hospital-acquired and community-associated methicillin-resistant (MRSA), which has markedly narrowed our options for treating life-threatening staph infections. Thus, there is an urgent need to develop novel, potent, preventive, and therapeutic agents. In our current study, we performed a whole-cell screening assay of synthetic libraries for antibacterial activity and identified a novel molecule, MZ-01. MZ-01 exhibited potent bactericidal activity against Gram-positive bacterial pathogens, including MRSA, , and at low concentrations. MZ-01 killed and lysed both the late exponential phase of an population and bacteria inside mammalian cells. Furthermore, MZ-01 exhibited low cytotoxicity. These results indicate that MZ-01 is a promising scaffold to guide the development of novel, potent antibacterial agents against multidrug-resistant Gram-positive bacterial pathogens such as MRSA.
新型抗生素类别的发现进展缓慢，且远远落后于细菌耐药性的发展速度。这种差距使我们处于越来越脆弱的境地，因为我们治疗耐抗生素感染的安全有效治疗选择正在耗尽。医院获得性和社区相关性耐甲氧西林金黄色葡萄球菌（MRSA）的出现和持续存在就是例证，这显著缩小了我们治疗危及生命的葡萄球菌感染的选择范围。因此，迫切需要开发新型、强效、预防性和治疗性药物。在我们目前的研究中，我们对合成文库进行了全细胞抗菌活性筛选试验，并鉴定出一种新型分子MZ - 01。MZ - 01在低浓度下对包括MRSA在内的革兰氏阳性细菌病原体表现出强效杀菌活性。MZ - 01能杀死并裂解金黄色葡萄球菌群体的指数后期阶段以及哺乳动物细胞内的细菌。此外，MZ - 01表现出低细胞毒性。这些结果表明，MZ - 01是一个有前景的框架，可用于指导开发针对多重耐药革兰氏阳性细菌病原体（如MRSA）的新型强效抗菌药物。
