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Silviavirus 噬菌体 ɸMR003 对源自人类的耐甲氧西林金黄色葡萄球菌具有广泛的宿主范围。

Silviavirus phage ɸMR003 displays a broad host range against methicillin-resistant Staphylococcus aureus of human origin.

机构信息

School of Life Science and Technology, Tokyo Institute of Technology, 4259J2-15 Nagatsuta-cho, Midori-ku, Yokohama, 226-8501, Japan.

Faculty of Chemical and Food Engineering, Institute of Technology of Cambodia, Russian Federation Blvd., P.O. Box 86, Phnom Penh, 12156, Cambodia.

出版信息

Appl Microbiol Biotechnol. 2019 Sep;103(18):7751-7765. doi: 10.1007/s00253-019-10039-2. Epub 2019 Aug 6.

Abstract

The emergence of life-threatening methicillin-resistant Staphylococcus aureus (MRSA) has led to increased interest in the use of bacteriophages as an alternative therapy to antibiotics. The success of phage therapy is greatly dependent on the selected phage possessing a wide host range. This study describes phage ɸMR003 isolated from sewage influent at a municipal wastewater treatment plant in Tokyo, Japan. ɸMR003 could infect 97% of 104 healthcare- and community-associated MRSA strains tested, compared with 73% for phage ɸSA012, which has a broad host range against bovine mastitis S. aureus. Genome analysis revealed that ɸMR003 belongs to the genus Silviavirus which has not been studied extensively. ɸMR003 recognizes and binds to wall teichoic acid (WTA) of S. aureus during infection. In silico comparisons of the genomes of ɸMR003 and ɸSA012 revealed that ORF117 and ORF119 of ɸMR003 are homologous to the putative receptor-binding proteins ORF103 and ORF105 of ɸSA012, with amino acid similarities of 75% and 72%, respectively. ORF104, which is an N-acetylglucosaminidase found in the ɸMR003 tail, may facilitate phage's infection onto the WTA-null S. aureus RN4220. The differences in tail and baseplate proteins may be key contributing factors to the different host specificities of ɸMR003 and ɸSA012. ɸMR003 showed strong adsorptivity, but not infectivity, against S. aureus SA003, which may be influenced by the bacterium's restriction modification system. This study expands our knowledge of the genomic diversity and host specificity of Silviavirus, which is a potential phage therapy candidate for MRSA infections.

摘要

具有生命威胁性的耐甲氧西林金黄色葡萄球菌 (MRSA) 的出现,促使人们对噬菌体作为抗生素替代疗法的应用产生了浓厚的兴趣。噬菌体疗法的成功在很大程度上取决于所选噬菌体具有广泛的宿主范围。本研究描述了从日本东京一家市立污水处理厂的污水进水口分离到的噬菌体 ɸMR003。与具有广泛宿主范围的针对牛乳腺炎金黄色葡萄球菌的噬菌体 ɸSA012 相比, ɸMR003 可以感染 97%测试的 104 株医疗保健和社区相关 MRSA 菌株,而 ɸSA012 只能感染 73%。基因组分析表明, ɸMR003 属于 Silviavirus 属,该属尚未得到广泛研究。 ɸMR003 在感染过程中识别并结合金黄色葡萄球菌的细胞壁磷壁酸 (WTA)。 ɸMR003 和 ɸSA012 的基因组序列比较表明, ɸMR003 的 ORF117 和 ORF119 与 ɸSA012 的假定受体结合蛋白 ORF103 和 ORF105 同源,氨基酸相似性分别为 75%和 72%。 ɸMR003 尾部的 ORF104 是一种 N-乙酰氨基葡萄糖苷酶,可能有助于噬菌体感染 WTA 缺失的金黄色葡萄球菌 RN4220。尾巴和基板蛋白的差异可能是 ɸMR003 和 ɸSA012 宿主特异性不同的关键因素。 ɸMR003 对金黄色葡萄球菌 SA003 表现出强烈的吸附性,但没有感染力,这可能受到细菌的限制修饰系统的影响。本研究扩展了我们对 Silviavirus 的基因组多样性和宿主特异性的认识,Silviavirus 是治疗耐甲氧西林金黄色葡萄球菌感染的潜在噬菌体治疗候选物。

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