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在对长尾噬菌体针对广谱多药耐药大肠杆菌的基因组分析中,发现了多种不同的感染和裂解机制。

Diverse infective and lytic machineries identified in genome analysis of tailed coliphages against broad spectrum multidrug-resistant Escherichia coli.

机构信息

Microbiology Fermentation and Biotechnology Division, ICAR-Central Institute of Fisheries Technology (ICAR-CIFT), Matsyapuri Post, Willingdon Island, Kochi, 682029, Kerala, India.

Visakhapatnam Research Centre of ICAR-Central Institute of Fisheries Technology, Visakhapatnam, 530003, Andhra Pradesh, India.

出版信息

Int Microbiol. 2023 Aug;26(3):459-469. doi: 10.1007/s10123-022-00310-4. Epub 2022 Dec 12.

DOI:10.1007/s10123-022-00310-4
PMID:36504140
Abstract

The emergence of multidrug-resistant (MDR) E. coli with deleterious consequences to the health of humans and animals has been attributed to the inappropriate use of antibiotics. Without effective antimicrobials, the success of modern medicine in treating infections would be at an increased risk. Bacteriophages could be used as an alternative to antibiotics for controlling the dissemination of MDR bacteria. However, before their use, the bacteriophages have to be assessed for the safety aspect. In this study, three broad host range highly virulent coliphage genomes were sequenced, characterized for infective and lytic potential, and checked for the presence of virulence and resistance genes. The genome sequencing indicated that coliphages ϕEC-S-21 and ϕEC-OE-11 belonged to Myoviridae, whereas coliphage ϕEC-S-24 belonged to the Autographiviridae family derived from the Podoviridae family. The genome size of the three coliphages ranged between 24 and 145 kb, with G + C content ranging between 37 and 51%. Coding sequences (CDS) ranged between 30 and 251 amino acids. The CDS were annotated and the proteins were categorized into different modules, viz., phage structural proteins, proteins associated with DNA replication, DNA modification, bacterial cell lysis, phage packaging, and uncharacterized proteins. The presence of tRNAs was detected only in coliphage ϕEC-OE-11. All three coliphages possessed diverse infective and lytic mechanisms, viz., lytic murein transglycosylase, peptidoglycan transglycosylase, n-acetylmuramoyl-l-alanine amidase, and putative lysozyme. Furthermore, the three coliphage genomes showed neither the presence of antibiotic resistance genes nor virulence genes, which makes them desirable candidates for use in phage therapy-based applications.

摘要

具有有害人类和动物健康后果的多药耐药(MDR)大肠杆菌的出现归因于抗生素的不当使用。如果没有有效的抗菌药物,现代医学在治疗感染方面的成功将面临更大的风险。噬菌体可以替代抗生素来控制 MDR 细菌的传播。然而,在使用噬菌体之前,必须评估其安全性。在这项研究中,对三个广泛宿主范围的高毒性噬菌体基因组进行了测序、鉴定了感染性和裂解潜力,并检查了毒力和耐药基因的存在。基因组测序表明,噬菌体 ϕEC-S-21 和 ϕEC-OE-11 属于肌尾噬菌体科,而噬菌体 ϕEC-S-24 属于来自尾噬菌体科的 Autographiviridae 科。三种噬菌体的基因组大小在 24 到 145 kb 之间,G+C 含量在 37 到 51%之间。编码序列(CDS)在 30 到 251 个氨基酸之间。对 CDS 进行了注释,并将蛋白质分为不同的模块,即噬菌体结构蛋白、与 DNA 复制、DNA 修饰、细菌细胞裂解、噬菌体包装和未鉴定蛋白相关的蛋白。只有噬菌体 ϕEC-OE-11 中检测到 tRNA。三种噬菌体都具有不同的感染和裂解机制,即裂解型粘肽转糖基酶、肽聚糖转糖基酶、N-乙酰基胞壁酰-L-丙氨酸酰胺酶和潜在的溶菌酶。此外,三种噬菌体基因组既没有抗生素耐药基因也没有毒力基因,这使它们成为噬菌体治疗应用的理想候选者。

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