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Novel antimicrobial peptide CPF ‐C1 analogs with superior stabilities and activities against multidrug‐resistant bacteria
Author(s) -
Xie Junqiu,
Zhao Qian,
Li Sisi,
Yan Zhibin,
Li Jing,
Li Yao,
Mou Lingyun,
Zhang Bangzhi,
Yang Wenle,
Miao Xiaokang,
Jiang Xianxing,
Wang Rui
Publication year - 2017
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12988
Subject(s) - antimicrobial , multiple drug resistance , bacteria , antimicrobial peptides , antibiotics , peptide , antibiotic resistance , chemistry , tryptophan , microbiology and biotechnology , in vivo , in vitro , biofilm , biology , amino acid , biochemistry , genetics
As numerous clinical isolates are resistant to most conventional antibiotics, infections caused by multidrug‐resistant bacteria are associated with a higher death rate. Antimicrobial peptides show great potential as new antibiotics. However, a major obstacle to the development of these peptides as useful drugs is their low stability. To overcome the problem of the natural antimicrobial peptide CPF ‐C1, we designed and synthesized a series of analogs. Our results indicated that by introducing lysine, which could increase the number of positive charges, and by introducing tryptophan, which could increase the hydrophobicity, we could improve the antimicrobial activity of the peptides against multidrug‐resistant strains. The introduction of d ‐amino acids significantly improved stability. Certain analogs demonstrated antibiofilm activities. In mechanistic studies, the analogs eradicated bacteria not just by interrupting the bacterial membranes, but also by linking to DNA , which was not impacted by known mechanisms of resistance. In a mouse model, certain analogs were able to significantly reduce the bacterial load. Among the analogs, CPF ‐9 was notable due to its greater antimicrobial potency in vitro and in vivo and its superior stability, lower hemolytic activity, and higher antibiofilm activity. This analog is a potential antibiotic candidate for treating infections induced by multidrug‐resistant bacteria.