Department of Medical Microbiology and Immunology, Medical School, University of Pécs, Szigeti st. 12., H-7624 Pécs, Hungary.
Institute of Food and Beverage Innovation, Food Microbiology, ZHAW School of Life Sciences and Facility Management, Einsiedlerstrasse 31, 8820 Wädenswil, Switzerland.
Biomed Res Int. 2020 Dec 22;2020:5463801. doi: 10.1155/2020/5463801. eCollection 2020.
Methicillin-resistant (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 , , showed a narrow host range and stable lytic activity without the emergence of resistant MRSA clones. Phylogenetic analysis showed that the newly isolated phage R4 belongs to the genus in 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.
耐甲氧西林金黄色葡萄球菌(MRSA)可引起从轻度到危及生命的各种感染。其增强的抗生素耐药性常常导致治疗失败,因此必须考虑替代的清除方法。控制 MRSA 感染的潜在候选者是噬菌体及其裂解酶,即溶菌素。在这项研究中,我们分离到了一种针对属于 ST45 流行病学组的医院获得性 MRSA 菌株的噬菌体。属于长尾噬菌体科的噬菌体 ,表现出狭窄的宿主范围和稳定的裂解活性,而没有产生耐药性的 MRSA 克隆。系统发育分析表明,新分离的 R4 噬菌体属于长尾噬菌体科的 属。对 R4 的 45kb 序列进行基因分析显示有 69 个 ORF。未观察到移动遗传元件的残余物和截短基因的痕迹。我们已经定位了新噬菌体的溶菌酶(N-乙酰基胞壁酰-L-丙氨酸酰胺酶)基因,该基因被扩增、克隆、表达和纯化。通过酶谱分析验证了其活性。我们的研究结果可能有助于开发针对主要克隆谱系和血清型的特异性抗 MRSA 噬菌体和噬菌体溶菌素治疗策略。