文献类型：期刊文献

英文题名：Two optimized antimicrobial peptides with therapeutic potential for clinical antibiotic-resistant Staphylococcus aureus

作者：Li, Chunlei[1,2];Zhu, Chengguang[3,4];Ren, Biao[3];Yin, Xin[1];Shim, Sang Hee[5,6];Gao, Yue[2];Zhu, Jianhua[2];Zhao, Peipei[1];Liu, Changheng[1];Yu, Rongmin[2];Xia, Xuekui[1];Zhang, Lixin[1,7]

机构：[1]Qilu Univ Technol, Biol Inst, Key Biosensor Lab Shandong Provinde, Shandong Acad Sci, Jinan 250103, Shandong, Peoples R China;[2]Jinan Univ, Biotechnol Inst Chinese Mat Med, 601 Huangpu Ave West, Guangzhou 510632, Guangdong, Peoples R China;[3]Sichuan Univ, State Key Lab Oral Dis, Chengdu 610041, Sichuan, Peoples R China;[4]Sichuan Univ, West China Hosp Stomatol, Dept Operat Dent & Endodont, Chengdu 610041, Sichuan, Peoples R China;[5]Duksung Womens Univ, Coll Pharm, Seoul 01369, South Korea;[6]Duksung Womens Univ, Innovat Drug Ctr, Seoul 01369, South Korea;[7]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2019

卷号：183

外文期刊名：EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000498308700020)】；

基金：We gratefully acknowledge the financial support of National Natural Science Foundation of China (No. 31770024, 81600858, 81870778, 31720103901, 31430002), National Key R&D Program of China (No. 2017YFF0209900), Ocean and Fisheries Science and Technology Development Projects of Guangdong (No. A201501C04), Major Science and Technology Projects/Significant New Drugs Creation of Guangdong (No. 2013A022100032), Natural Science Foundation from Shandong Province (No. ZR2017MH025, ZR2017ZB0206), and Taishan Scholars Program of Shandong Province for Lixin Zhang, the Youth Fund of Shandong Academy of Sciences (2018QN0029).

语种：英文

外文关键词：Optimized antimicrobial peptide; Anti-MRSA; Anti-biofilm; SEM; qRT-PCR

摘要：The rapid increase of Methicillin-resistant Staphylococcus aureus (MRSA) infections and the cross-resistance of MRSA to other antibiotics create an urgent demand for new therapeutic agents. Antimicrobial peptides (AMPs) are one of the most promising options for next-generation antibiotics. In this study, novel peptides were designed based on antimicrobial peptide fragments derived from Aristicluthys nobilia interferon-I to promote anti-MRSA activity and decrease adverse effects. Design strategies included substitutions of charged or hydrophobic amino acid residues for noncharged polar residues to promote amphipathicity. Two designed peptides, P5 (YIRKIRRFFKKLKKILKK-NH2) and P9 (SYER-KINRHFTLKKNLKKK-NH2), showed potent antimicrobial activities against both sensitive Staphylococcus aureus clinical isolates and MRSA strains without significant hemolysis or cytotoxicity to human hemocytes and renal epithelial cells. Scanning Electronic Microscopy (SEM) and qRT-PCR were employed to investigate the effects of P5 and P9 on S. aureus biofilm formation, morphology, and virulence-related gene expression. P5 and P9 significantly inhibited the biofilm and destroyed the cell membrane integrity, in addition to down-regulating several virulence factor genes and biofilm formation-related genes including spa, hld, and sdrC. P5 and P9 could be promising candidate antibacterial agents for the treatment of MRSA infections. (C) 2019 Elsevier Masson SAS. All rights reserved.