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康涅狄格大学金奖演讲——伯克霍尔德氏菌复合群噬菌体的基因组分析与修饰。

Cangene gold medal award lecture - Genomic analysis and modification of Burkholderia cepacia complex bacteriophages.

机构信息

6-008 Centennial Centre for Interdisciplinary Science, Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E9, Canada.

出版信息

Can J Microbiol. 2012 Mar;58(3):221-35. doi: 10.1139/w11-135. Epub 2012 Feb 17.

DOI:10.1139/w11-135
PMID:22339239
Abstract

The Burkholderia cepacia complex (Bcc) is a group of 17 Gram-negative predominantly environmental bacterial species that cause potentially fatal opportunistic infections in cystic fibrosis (CF) patients. Although its prevalence in these individuals is lower than that of Staphylococcus aureus and Pseudomonas aeruginosa , the Bcc remains a serious problem in the CF community because of the pathogenicity, transmissibility, and inherent antibiotic resistance of these organisms. An alternative treatment for Bcc infections that is currently being developed is phage therapy, the clinical use of viruses that infect bacteria. To assess the suitability of individual phage isolates for therapeutic use, the complete genome sequences of a panel of Bcc-specific phages were determined and analyzed. These sequences encode a broad range of proteins with a gradient of relatedness to phage and bacterial gene products from Burkholderia and other genera. The majority of these phages were found not to encode virulence factors, and despite their predominantly temperate nature, a proof-of-principle experiment has shown that they may be modified to a lytic form. Both the genomic characterization and subsequent engineering of Bcc-specific phages are fundamental to the development of an effective phage therapy strategy for these bacteria.

摘要

洋葱伯克霍尔德氏菌复合体(Bcc)是一组 17 种革兰氏阴性主要为环境细菌物种,它们会导致囊性纤维化(CF)患者发生潜在致命的机会性感染。尽管其在这些个体中的流行率低于金黄色葡萄球菌和铜绿假单胞菌,但由于这些生物体的致病性、传染性和固有抗生素耐药性,Bcc 仍然是 CF 社区的一个严重问题。目前正在开发的针对 Bcc 感染的替代治疗方法是噬菌体治疗,即临床使用感染细菌的病毒。为了评估单个噬菌体分离物用于治疗的适用性,确定并分析了一组 Bcc 特异性噬菌体的完整基因组序列。这些序列编码了广泛的蛋白质,其与噬菌体和来自伯克霍尔德氏菌和其他属的细菌基因产物的相关性呈梯度分布。这些噬菌体中的大多数未编码毒力因子,尽管它们主要是温和的,但一项原理验证实验表明,它们可以被修饰为裂解形式。Bcc 特异性噬菌体的基因组特征分析和后续工程是为这些细菌开发有效噬菌体治疗策略的基础。

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