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编码逆转录酶介导的嗜性转换盒的博德特氏菌噬菌体的基因组和遗传分析。

Genomic and genetic analysis of Bordetella bacteriophages encoding reverse transcriptase-mediated tropism-switching cassettes.

作者信息

Liu Minghsun, Gingery Mari, Doulatov Sergei R, Liu Yichin, Hodes Asher, Baker Stephen, Davis Paul, Simmonds Mark, Churcher Carol, Mungall Karen, Quail Michael A, Preston Andrew, Harvill Eric T, Maskell Duncan J, Eiserling Frederick A, Parkhill Julian, Miller Jeff F

机构信息

Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, California 90095, USA.

出版信息

J Bacteriol. 2004 Mar;186(5):1503-17. doi: 10.1128/JB.186.5.1503-1517.2004.

DOI:10.1128/JB.186.5.1503-1517.2004
PMID:14973019
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC344406/
Abstract

Liu et al. recently described a group of related temperate bacteriophages that infect Bordetella subspecies and undergo a unique template-dependent, reverse transcriptase-mediated tropism switching phenomenon (Liu et al., Science 295: 2091-2094, 2002). Tropism switching results from the introduction of single nucleotide substitutions at defined locations in the VR1 (variable region 1) segment of the mtd (major tropism determinant) gene, which determines specificity for receptors on host bacteria. In this report, we describe the complete nucleotide sequences of the 42.5- to 42.7-kb double-stranded DNA genomes of three related phage isolates and characterize two additional regions of variability. Forty-nine coding sequences were identified. Of these coding sequences, bbp36 contained VR2 (variable region 2), which is highly dynamic and consists of a variable number of identical 19-bp repeats separated by one of three 5-bp spacers, and bpm encodes a DNA adenine methylase with unusual site specificity and a homopolymer tract that functions as a hotspot for frameshift mutations. Morphological and sequence analysis suggests that these Bordetella phage are genetic hybrids of P22 and T7 family genomes, lending further support to the idea that regions encoding protein domains, single genes, or blocks of genes are readily exchanged between bacterial and phage genomes. Bordetella bacteriophages are capable of transducing genetic markers in vitro, and by using animal models, we demonstrated that lysogenic conversion can take place in the mouse respiratory tract during infection.

摘要

刘等人最近描述了一组感染博德特氏菌亚种的相关温和噬菌体,它们会经历一种独特的模板依赖性、逆转录酶介导的嗜性转换现象(刘等人,《科学》295:2091 - 2094,2002年)。嗜性转换是由于在决定宿主细菌受体特异性的mtd(主要嗜性决定因子)基因的VR1(可变区1)片段的特定位置引入了单核苷酸替换。在本报告中,我们描述了三种相关噬菌体分离株的42.5至42.7 kb双链DNA基因组的完整核苷酸序列,并对另外两个可变区进行了特征分析。鉴定出了49个编码序列。在这些编码序列中,bbp36包含VR2(可变区2),其高度动态,由可变数量的相同19 bp重复序列组成,这些重复序列由三种5 bp间隔序列之一隔开,并且bpm编码一种具有不寻常位点特异性的DNA腺嘌呤甲基转移酶以及一个作为移码突变热点的同聚物序列。形态学和序列分析表明,这些博德特氏菌噬菌体是P22和T7家族基因组的遗传杂种,这进一步支持了编码蛋白质结构域、单个基因或基因块的区域在细菌和噬菌体基因组之间容易交换的观点。博德特氏菌噬菌体能够在体外转导遗传标记,并且通过使用动物模型,我们证明了在感染期间小鼠呼吸道中可发生溶原性转换。