Department of Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, United Kingdom.
Microb Pathog. 2010 May;48(5):191-5. doi: 10.1016/j.micpath.2010.01.005. Epub 2010 Jan 22.
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 7x10(4)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.
需要开发针对鼠疫耶尔森菌（鼠疫的病原体，也是一种潜在的生物恐怖主义制剂）的有效对策。已证实，缺失参与鸟嘌呤生物合成的 guaBA 基因的沙门氏菌和志贺氏菌在体内的毒力减弱。在本研究中，我们试图确定 guaBA 操纵子的缺失是否会使鼠疫耶尔森菌对鸟嘌呤产生营养缺陷并丧失毒力；这样的菌株可以作为一种活的减毒鼠疫疫苗候选物。通过特异性缺失 guaBA 操纵子的一段序列，产生了一种鸟嘌呤营养缺陷型鼠疫耶尔森菌突变株，该突变株在鼠疫耶尔森菌感染的小鼠模型中高度减毒。此外，通过静脉途径给予单次剂量 7x10(4)CFU 的疫苗接种，小鼠可完全免受随后用鼠疫耶尔森菌亲本菌株进行的致死性攻击。这些发现确定了 guaBA 是用于缺失以生成活的减毒鼠疫疫苗的靶标。
