中文摘要:耐甲氧西林金黄色葡萄球菌(MRSA)能引起多种感染,情况从轻微到危及生命。其增强的抗生素耐药性往往难以治疗,因此急需研究替代根治的方法。控制MRSA感染的潜在候选物是噬菌体及其裂解酶。本研究分离了一株抗院内获得性MRSA的噬菌体,该菌株属于ST45流行病学组。该噬菌体属于尾状病毒目,长尾噬菌体科,宿主范围窄,裂解酶活性稳定,未出现耐药MRSA无性系;系统发育分析表明,新分离的葡萄球菌噬菌体R4属于长尾噬菌体科Triavirus病毒属;对R4的45kb序列进行遗传分析,发现了69个ORF;未发现可移动遗传元件残余和截短基因痕迹。本研究定位了经扩增、克隆、表达和纯化后的新噬菌体的细胞裂解酶(N-乙酰壁氨酰-L-丙氨酸酰胺酶)基因,并通过酶谱分析证实了其活性。本研究结果可针对MRSA主要的克隆谱系和血清型开发具有特异抗性的噬菌体及噬菌体细胞裂解酶治疗方案。
外文摘要:Methicillin-resistant Staphylococcus aureus (MRSA) can cause a wide range of infections from mild to life-threatening conditions. Its enhanced antibiotic resistance often leads to therapeutic failures and therefore alternative eradication methods must be considered. Potential candidates to control MRSA infections are bacteriophages and their lytic enzymes, lysins. In this study, we isolated a bacteriophage against a nosocomial MRSA strain belonging to the ST45 epidemiologic group. The phage belonging to Caudovirales, Siphoviridae, showed a narrow host range and stable lytic activity without the emergence of resistant MRSA clones. Phylogenetic analysis showed that the newly isolated Staphylococcus phage R4 belongs to the Triavirus genus in Siphoviridae family. Genetic analysis of the 45 kb sequence of R4 revealed 69 ORFs. No remnants of mobile genetic elements and traces of truncated genes were observed. We have localized the lysin (N-acetylmuramoyl-L-alanine amidase) gene of the new phage that was amplified, cloned, expressed, and purified. Its activity was verified by zymogram analysis. Our findings could potentially be used to develop specific anti-MRSA bacteriophage- and phage lysin-based therapeutic strategies against major clonal lineages and serotypes.
作者:Pertics, BZ;Szenasy, D;Dunai, D;Born, Y;Fieseler, L;Kovacs, T;Schneider, G
作者单位:Univ Pecs;ZHAW Sch Life Sci & Facil Management;Enviroinvest Corp
期刊名称:BIOMED RESEARCH INTERNATIONAL
期刊影响因子:2.776
出版年份:2020
出版刊次:
点击下载:一种抗ST45院内获得性耐甲氧西林金黄色葡萄球菌的新型裂解性噬菌体的分离