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支气管败血波氏杆菌减毒代谢突变株的构建及特性鉴定在疫苗学中的应用。

Development and characterization of attenuated metabolic mutants of Bordetella bronchiseptica for applications in vaccinology.

机构信息

Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, D-38124 Braunschweig, Germany.

出版信息

Environ Microbiol. 2013 Jan;15(1):64-76. doi: 10.1111/j.1462-2920.2012.02779.x. Epub 2012 Jun 7.

DOI:10.1111/j.1462-2920.2012.02779.x
PMID:22676396
Abstract

Bordetella bronchiseptica is an important pathogen causing a number of veterinary respiratory syndromes in agriculturally important and food-producing confinement-reared animals, resulting in great economic losses annually amounting to billions of euros worldwide. Currently available live vaccines are incompletely satisfactory in terms of efficacy and safety. An efficient vaccine for livestock animals would allow reducing the application of antibiotics, thereby preventing the massive release of pharmaceuticals into the environment. Here, we describe two new potential vaccine strains based on the BB7865 strain. Two independent attenuating mutations were incorporated by homologous recombination in order to make negligible the risk of recombination and subsequent reversion to the virulent phenotype. The mutations are critical for bacterial metabolism, resistance to oxidative stress, intracellular survival and in vivo persistence. The resulting double mutants BB7865 risA aroA and BB7865 risA dapE were characterized as promising vaccine candidates, which are able to confer protection against colonization of the lower respiratory tract after sublethal challenge with the wild-type strain.

摘要

支气管败血波氏杆菌是一种重要的病原体,可引起许多农业上重要的和在封闭饲养条件下生产的食用动物的呼吸道综合征,每年在全球造成数十亿欧元的巨大经济损失。目前可用的活疫苗在效力和安全性方面并不完全令人满意。一种针对牲畜的有效疫苗将允许减少抗生素的应用,从而防止大量药物释放到环境中。在这里,我们描述了两种基于 BB7865 株的新的潜在疫苗株。通过同源重组引入了两个独立的减毒突变,以将重组和随后回复为毒力表型的风险降到最低。这些突变对细菌代谢、耐氧化应激、细胞内存活和体内持久性至关重要。由此产生的双突变体 BB7865 risA aroA 和 BB7865 risA dapE 被表征为有前途的疫苗候选物,能够在亚致死性野生型菌株攻毒后,防止下呼吸道定植。

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Development and characterization of attenuated metabolic mutants of Bordetella bronchiseptica for applications in vaccinology.支气管败血波氏杆菌减毒代谢突变株的构建及特性鉴定在疫苗学中的应用。
Environ Microbiol. 2013 Jan;15(1):64-76. doi: 10.1111/j.1462-2920.2012.02779.x. Epub 2012 Jun 7.
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