Design and pharmacodynamics of recombinant fungus defensin nzl with improved activity against staphylococcus hyicus in vitro and in vivo
文献类型: 外文期刊
作者: Liu He;Yang Na;Teng Da;Mao Ruoyu;Hao Ya;Ma Xuanxuan;Wang Jianhua
作者机构:
关键词: Antimicrobial mechanism; Efficacy in vivo; Fungal defensin; Peptide design; S. hyicus
期刊名称: International Journal of Molecular Sciences
ISSN: 1661-6596
年卷期: 2021 年 22 卷 11 期
页码:
收录情况: JCR(2021版)
摘要: Staphylococcus hyicus is recognized as a leading pathogen of exudative epidermitis in modern swine industry. Antimicrobial peptides are attractive candidates for development as potential therapeutics to combat the serious threats of the resistance of S. hyicus. In this study, a series of derivatives were designed based on the NZ2114 template with the aim of obtaining peptides with more potent antimicrobial activity through changing net positive charge or hydrophobicity. Among them, a variant designated as NZL was highly expressed in Pichia pastoris (P. pastoris) with total secreted protein of 1505 mg/L in a 5-L fermenter and exhibited enhanced antimicrobial activity relative to parent peptide NZ2114. Additionally, NZL could kill over 99% of S. hyicus NCTC10350 in vitro within 8 h and in Hacat cells. The results of membrane permeabilization assay, morphological observations, peptide localization assay showed that NZL had potent activity against S. hyicus, which maybe kill S. hyicus through action on the cell wall. NZL also showed an effective therapy in a mouse peritonitis model caused by S. hyicus, superior to NZ2114 or ceftriaxone. Overall, these findings can contribute to explore a novel potential candidate against S. hyicus infections. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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