中文摘要：艰难梭菌是一种形成芽孢的肠道病原体，可引起腹泻和结肠炎，危及生命。抗生素引起的微生物干扰与艰难梭菌感染的易感性、传播和复发有关。因此,迫切需要新的治疗方法来预防艰难梭菌生长、孢子萌发。近年来，噬菌体衍生的内溶素及其衍生物显示出新型抗菌剂的潜力。本研究重组表达并鉴定了一种艰难梭菌噬菌体phiMMP01的细胞壁水解酶（CWH）溶酶。全长CWH显示出对选定艰难梭菌的溶解活性。而去除N-末端细胞壁结合域产生的CWH351-656，使得活性增加和/或扩大了裂解谱。与共生梭状芽孢杆菌和其他细菌相比，保留了艰难梭菌的特异性。不出所料，假定的细胞壁结合域CWH1-350完全失活。还发现CWH351-656对艰难梭菌芽孢生长具有抑制作用。可见，CWH351-656作为一种抗艰难梭菌感染的抗菌药物潜力巨大。
外文摘要：Clostridioides difficile is a spore-forming enteric pathogen causing life-threatening diarrhoea and colitis. Microbial disruption caused by antibiotics has been linked with susceptibility to, and transmission and relapse of, C. difficile infection. Therefore, there is an urgent need for novel therapeutics that are effective in preventing C. difficile growth, spore germination, and outgrowth. In recent years bacteriophage-derived endolysins and their derivatives show promise as a novel class of antibacterial agents. In this study, we recombinantly expressed and characterized a cell wall hydrolase (CWH) lysin from C. difficile phage, phiMMP01. The full-length CWH displayed lytic activity against selected C. difficile strains. However, removing the N-terminal cell wall binding domain, creating CWH351-656, resulted in increased and/or an expanded lytic spectrum of activity. C. difficile specificity was retained versus commensal clostridia and other bacterial species. As expected, the putative cell wall binding domain, CWH1-350, was completely inactive. We also observe the effect of CWH351-656 on preventing C. difficile spore outgrowth. Our results suggest that CWH351-656 has therapeutic potential as an antimicrobial agent against C. difficile infection.
外文关键词：Clostridioides difficile infection；endolysin；antimicrobial agent；antimicrobial resistance；enteric pathogen；antibiotics
作者：Mondal, SI；Akter, A；Draper, LA；Ross, RP；Hill, C
作者单位：Univ Coll Cork；Shahjalal Univ Sci & Technol
期刊名称：INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
期刊影响因子：4.556
出版年份：2021
出版刊次：11
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