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用于噬菌体疗法的噬菌体的分离与鉴定

Isolation and Characterization of Phages for Phage Therapy.

作者信息

Townsend Eleanor M, Kelly Lucy, Gannon Lucy, Muscatt George, Dunstan Rhys, Michniewski Slawomir, Sapkota Hari, Kiljunen Saija J, Kolsi Anna, Skurnik Mikael, Lithgow Trevor, Millard Andrew D, Jameson Eleanor

机构信息

Department of Microbiology and Virology, School of Life Sciences, Gibbet Hill Campus, The University of Warwick, Coventry, United Kingdom.

Department of Genetics, University of Leicester, Leicester, United Kingdom.

出版信息

Phage (New Rochelle). 2021 Mar 1;2(1):26-42. doi: 10.1089/phage.2020.0046. Epub 2021 Mar 17.

Abstract

is a clinically important pathogen causing a variety of antimicrobial resistant infections in both community and nosocomial settings, particularly pneumonia, urinary tract infection, and sepsis. Bacteriophage (phage) therapy is being considered a primary option for the treatment of drug-resistant infections of these types. We report the successful isolation and characterization of 30 novel, genetically diverse phages. The isolated phages span six different phage families and nine genera, representing both lysogenic and lytic lifestyles. Individual phage isolates infected up to 11 of the 18 capsule types tested, and all 18 capsule-types were infected by at least one of the phages. Of the -infecting phages presented in this study, the lytic phages are most suitable for phage therapy, based on their broad host range, high virulence, short lysis period and given that they encode no known toxin or antimicrobial resistance genes. Phage isolates belonging to the and genera were deemed most suitable for phage therapy based on our characterization. Importantly, when applied alone, none of the characterized phages were able to suppress the growth of for more than 12 h, likely due to the inherent ease of to generate spontaneous phage-resistant mutants. This indicates that for successful phage therapy, a cocktail of multiple phages would be necessary to treat infections.

摘要

是一种具有临床重要性的病原体,在社区和医院环境中都会引起多种耐药性感染,尤其是肺炎、尿路感染和败血症。噬菌体疗法正被视为治疗这类耐药性感染的主要选择。我们报告了30种新型、基因多样的噬菌体的成功分离和特性鉴定。分离出的噬菌体跨越六个不同的噬菌体家族和九个属,代表了溶原性和裂解性两种生活方式。单个噬菌体分离株可感染所测试的18种荚膜类型中的多达11种,并且所有18种荚膜类型都至少被一种噬菌体感染。在本研究中呈现的感染性噬菌体中,裂解性噬菌体因其广泛的宿主范围、高毒力、短裂解期以及它们不编码已知毒素或抗菌抗性基因,而最适合用于噬菌体疗法。根据我们的特性鉴定,属于和属的噬菌体分离株被认为最适合用于噬菌体疗法。重要的是,单独应用时,所鉴定的噬菌体均不能抑制超过12小时,这可能是由于其固有地易于产生自发的噬菌体抗性突变体。这表明,为了成功进行噬菌体疗法,需要多种噬菌体的混合物来治疗感染。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d043/9041620/373c451c8b30/phage.2020.0046_figure1.jpg

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