A Yersinia pestis guaBA mutant is attenuated in virulence and provides protection against plague in a mouse model of infection.
A Yersinia pestis guaBA mutant is attenuated in virulence and provides protection against plague in a mouse model of infection.
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DOI：
10.1016/j.micpath.2010.01.005
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发表时间：
2010-05
影响因子：
3.8
通讯作者：
Atkins HS
中科院分区：
文献类型：
--
作者：
Oyston PC;Mellado-Sanchez G;Pasetti MF;Nataro JP;Titball RW;Atkins HS
鼠疫耶尔森菌是鼠疫的病原体，也是潜在的生物恐怖分子，因此需要制定有效的对策。沙门氏菌和志贺氏菌。已经显示在体内减弱了参与鸟嘌呤生物合成的guaBA基因中缺失的突变。在这项研究中，我们试图确定删除guaBA操纵子是否会使Y。鼠疫菌鸟嘌呤营养缺陷型且无毒力;这样的菌株可以用作活的减毒鼠疫疫苗候选物。解脂耶通过特异性缺失guaBA操纵子的一个片段产生鼠疫guaBA突变体，产生鸟嘌呤营养缺陷型，其在鼠疫耶尔森氏菌小鼠模型中高度减毒。鼠疫感染此外，通过静脉途径单次接种7×104 CFU的小鼠完全保护其免受随后的Y.鼠疫亲本菌株这些发现将guaBA鉴定为缺失的靶标以产生减毒活鼠疫疫苗。
There is a need to develop effective countermeasures for Yersinia pestis, the etiologic agent of plague and a potential bioterrorism agent. Salmonella and Shigella spp. deleted in the guaBA genes involved in guanine biosynthesis have been shown to be attenuated in vivo. In this study, we sought to determine whether deletion of the guaBA operon would render Y. pestis auxotrophic for guanine and avirulent; such a strain could serve as a live attenuated plague vaccine candidate. A Y. pestis guaBA mutant was generated by specific deletion of a segment of the guaBA operon, producing a guanine auxotroph that was highly attenuated in a mouse model of Y. pestis infection. Furthermore, mice vaccinated with a single dose of 7×104 CFU via the intravenous route were fully protected against subsequent lethal challenge with the Y. pestis parental strain. These findings identify guaBA as a target for deletion to generate a live attenuated plague vaccine.
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影响因子：
56.9
作者：
Guo, L;Lim, KB;Miller, SI
通讯作者：
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Santiago AE;Cole LE;Franco A;Vogel SN;Levine MM;Barry EM
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