Chao Zhong: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China; School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
Fangyan Zhang: School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
Jia Yao: The First Hospital of Lanzhou University, Lanzhou 730000, China.
Yuewen Zhu: School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
Ningyi Zhu: School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
Yun Zhang: School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
Hui Liu: School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
Sanhu Gou: School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
Jingman Ni: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China; School of Pharmacy, Lanzhou University, Lanzhou 730000, China; State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macao 999078, China. Electronic address: nijm@lzu.edu.cn.
In response to the dramatically increasing antimicrobial resistance, a series of new symmetric peptides were designed and synthesized in this study by a "WWW" motif as the symmetric center, arginine as the positive charge amino acid and the terminus symmetrically tagged with hydrophobic amino acids. Amongst the new symmetric peptide FRRW (FRRWWWRRF-NH) presented the highest cell selectivity for bacteria over mammalian cell and exerted excellent antimicrobial potential against a broad of bacteria, especially difficult-to-kill multidrug-resistant strains clinical isolates. FRRW also displayed perfect stability in physiological salt ions and rapid killing speed as well as acted on multiple mechanisms including non-receptor mediated membrane and intra-molecular mechanisms. Importantly, FRRW emerged a low tendency of resistance in contrast to traditional antibiotics ciprofloxacin and gentamicin. What's more, FRRW could resist or alleviate or even reverse the ciprofloxacin- and gentamicin-resistance by changing the permeability of bacterial membrane and inhibiting the efflux pumps of bacteria. Furthermore, FRRW exhibited remarkable effectiveness and higher safety in vivo than polymyxin B. In summary, the new symmetric peptide FRRW was promised to be as a new antimicrobial candidate for overcoming the increasing bacterial resistance.
