Shang Lu, Wu Yuting, Wei Nan, Yang Fayu, Wang Mi, Zhang Lifang, Fei Chenzhong, Liu Yingchun, Xue Feiqun, Gu Feng
Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.
Key Laboratory of Veterinary Chemical Drugs and Pharmaceutics, Ministry of Agriculture and Rural Affairs, Shanghai 200241, China.
ACS Appl Mater Interfaces. 2022 Jan 12;14(1):245-258. doi: 10.1021/acsami.1c19305. Epub 2021 Dec 29.
The emergence of multidrug-resistant microorganisms has been termed one of the most common global health threats, emphasizing the discovery of new antibacterial agents. To address this issue, we engineered peptides harboring "RWWWR" as a central motif plus arginine (R) end-tagging and then tested them and . Our results demonstrate that Pep 6, one of the engineered peptides, shows great potential in combating bacteremia and the skin burn infection model, which induces a 62-90% reduction in bacterial burden. Remarkably, after long serial passages of and for 30 days, Pep 6 is still highly efficient in killing pathogens, compared with 64- and 128-fold increase in minimal inhibitory concentrations (MICs) for vancomycin and polymyxin B, respectively. We also found that Pep 6 exhibited robust biofilm-inhibiting activity and eliminated 61.33% of the mature methicillin-resistant (MRSA) biofilm with concentration in the MIC level. These results suggest that the RWWWR motif and binding of arginine end-tagging could be harnessed as a new agent for combating multidrug-resistant bacteria.
多重耐药微生物的出现被称为最常见的全球健康威胁之一，这凸显了新型抗菌药物的发现。为解决这一问题，我们设计了以“RWWWR”为中心基序并带有精氨酸（R）末端标记的肽段，然后对其进行了测试。我们的结果表明，设计的肽段之一Pep 6在对抗菌血症和皮肤烧伤感染模型方面显示出巨大潜力，可使细菌载量降低62%至90%。值得注意的是，在经过30天的长期连续传代后，与万古霉素和多粘菌素B的最低抑菌浓度（MIC）分别增加64倍和128倍相比，Pep 6在杀灭病原体方面仍然高效。我们还发现Pep 6表现出强大的生物膜抑制活性，在MIC水平浓度下可消除61.33%的成熟耐甲氧西林金黄色葡萄球菌（MRSA）生物膜。这些结果表明，RWWWR基序和精氨酸末端标记的结合可作为对抗多重耐药细菌的新型药物。
