文献类型：期刊文献

英文题名：Development of Antibacterial Peptides with Membrane Disruption and Folate Pathway Inhibitory Activities against Methicillin-Resistant Staphylococcus aureus

作者：Li, Chunlei[1,2];Zhou, Ziyi[3,4];Wang, Weitao[1];Zhao, Yanqiu[1];Yin, Xin[1];Meng, Yiwei[1];Zhao, Peipei[1];Wang, Mengmeng[1];Liu, Xueting[5];Wang, Xinye[5];Wang, Shenlin[5];Ren, Biao[3,4];Zhang, Lixin[5];Xia, Xuekui[1]

机构：[1]Qilu Univ Technol, Shandong Acad Sci, Biol Inst, Shandong Prov Key Lab Biomfg, Jinan 250103, Peoples R China;[2]Shandong Univ, Qilu Hosp, Cheloo Coll Med, Dept Pharm, Jinan 250012, Peoples R China;[3]Sichuan Univ, West China Sch Stomatol, State Key Lab Oral Dis, Chengdu 610041, Peoples R China;[4]Sichuan Univ, Natl Clin Res Ctr Oral Dis, West China Sch Stomatol, Chengdu 610041, Peoples R China;[5]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2024

卷号：67

期号：2

起止页码：1044

外文期刊名：JOURNAL OF MEDICINAL CHEMISTRY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001151564900001)】；

基金：The authors gratefully acknowledge the Funding Key R&D Program of Shandong Province (2022SFGC0105), National Natural Science Foundation of China (82003910), Innovation and Development Joint Fund of Natural Science Foundation from Shandong Province (ZR2021LSW022), Exploration Innovation Team (2021GXRC062), Jinan Talent Project for Universities(202228088), Young Taishan Scholarship to X.X. (tsqn202103100), Key Innovation Project of Qilu University of Technology (Shandong Academy of Sciences) (2022JBZ01-06), and International cooperation Project of Qilu University of Technology (Shandong Academy of Sciences) (2022GH024).

语种：英文

摘要：Antimicrobial peptides (AMPs) offer an opportunity to overcome multidrug resistance. Here, novel peptides were designed based on AMP fragments derived from sea cucumber hemolytic lectin to enhance anti-methicillin-resistant Staphylococcus aureus (MRSA) activity with less side effects. Two designed peptides, CGS19 (LARVARRVIRFIRRAW-NH2) and CGS20 (RRRLARRLIFFIRRAW-NH2), exhibited strong antibacterial activities against clinically isolated MRSA with MICs of 3-6 mu M, but no obvious cytotoxicity was observed. Consistently, CGS19 and CGS20 exerted rapid bactericidal activity and effectively induced 5.9 and 5.8 log reduction of MRSA counts in mouse subeschar, respectively. Further, CGS19 and CGS20 kill bacteria not only through disturbing membrane integrity but also by binding formate-tetrahydrofolate ligase, a key enzyme in the folate metabolism pathway, thereby inhibiting the folate pathway of MRSA. CGS19 and CGS20 are promising lead candidates for drug development against MRSA infection. The dual mechanisms on the identical peptide sequence or scaffold might be an underappreciated manner of treating life-threatening pathogens.