Novel Enterococcus phage BUCT630: Isolation and genomic insights targeting drug-resistant Enterococcus faecium in vitro and in vivo

IF 3.5 3区 医学 Q3 IMMUNOLOGY
Zakirullah , Rashid Ahmad , Amna Shafqat , Mengzhe Li , Yigang Tong
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Abstract

The antibiotic-resistant Enterococcus faecium (E. faecium) is a significant health issue requiring alternative therapies. Phages could be an alternative to antibiotics and have promising activity in both in vitro and in vivo experiments. Here, we isolated and characterized a new lytic phage, BUCT630, from hospital sewage water targeting antibiotic-resistant E. faecium. Physiological characterization revealed that BUCT630 had a long adsorption time (50 min) and moderate burst size (130 PFU/cell), had relatively favourable stability in both acidic and alkaline environments, and withstand 50°C high temperature. Transmission electron microscopy (TEM) revealed that phage BUCT630 belongs to the unclassified Caudoviricetes through a phylogenetic tree based on a terminase large subunit and whole genome sequence. The host range was comparatively broad and can lyse 8 of 18 Enterococcus strains. Through BLASTn analysis, BUCT630 had 69% query coverage and 89% sequence identity with other phages in the database. The genomic analysis disclosed that phage BUCT630 is linear dsDNA with 41,942 bp having 35% GC content and comprises 61 open reading frames (ORF) free from antibiotic and virulence genes. Furthermore, BUCT630 in vitro could efficiently inhibit the E. faecium growth, and in vivo, it increased the survival rate to 90% in the Galerria mellonela model. Our findings revealed that BUCT630 is a promising therapeutic option for combating antibiotic resistant E. faecium infections.

Abstract Image

新型肠球菌噬菌体BUCT630:体外和体内针对耐药屎肠球菌的分离和基因组研究
耐抗生素的屎肠球菌(E. faecium)是一个重要的健康问题,需要替代疗法。噬菌体可以作为抗生素的替代品,在体外和体内实验中都具有良好的活性。在这里,我们从医院污水中分离并鉴定了一种新的裂解噬菌体BUCT630,该噬菌体靶向耐药粪肠杆菌。生理特性表明,BUCT630具有较长的吸附时间(50 min)和中等的爆发大小(130 PFU/cell),在酸性和碱性环境中均具有较好的稳定性,耐50℃高温。透射电子显微镜(TEM)显示,基于末端酶大亚基和全基因组序列的系统发育树显示,噬菌体BUCT630属于未分类的尾状菌门。宿主范围较广,可溶溶18株肠球菌中的8株。通过BLASTn分析,BUCT630与数据库中其他噬菌体的查询覆盖率为69%,序列一致性为89%。基因组分析表明,噬菌体BUCT630为41,942 bp的线性dsDNA, GC含量为35%,包含61个不含抗生素和毒力基因的开放阅读框(ORF)。此外,but630在体外能有效抑制粪肠球菌的生长,在体内可将大鼠galeria mellonela模型的存活率提高到90%。我们的研究结果表明,BUCT630是一种很有希望的治疗选择,用于对抗抗生素耐药粪肠杆菌感染。
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来源期刊
Microbial pathogenesis
Microbial pathogenesis 医学-免疫学
CiteScore
7.40
自引率
2.60%
发文量
472
审稿时长
56 days
期刊介绍: Microbial Pathogenesis publishes original contributions and reviews about the molecular and cellular mechanisms of infectious diseases. It covers microbiology, host-pathogen interaction and immunology related to infectious agents, including bacteria, fungi, viruses and protozoa. It also accepts papers in the field of clinical microbiology, with the exception of case reports. Research Areas Include: -Pathogenesis -Virulence factors -Host susceptibility or resistance -Immune mechanisms -Identification, cloning and sequencing of relevant genes -Genetic studies -Viruses, prokaryotic organisms and protozoa -Microbiota -Systems biology related to infectious diseases -Targets for vaccine design (pre-clinical studies)
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