Francisella tularensis tmRNA system mutants are vulnerable to stress, avirulent in mice, and provide effective immune protection.
Francisella tularensis tmRNA system mutants are vulnerable to stress, avirulent in mice, and provide effective immune protection.
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DOI：
10.1111/j.1365-2958.2012.08093.x
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发表时间：
2012-07
影响因子：
3.6
通讯作者：
Karzai AW
中科院分区：
文献类型：
--
作者：
Svetlanov A;Puri N;Mena P;Koller A;Karzai AW
通过靶向灭活的ssrA和smpB基因，我们建立的反式翻译过程是必要的正常生长，适应细胞应激，和细菌病原体土拉弗朗西斯菌的毒力。突变细菌生长较慢，对热和冷冲击的抵抗力降低，对氧化应激和亚致死浓度的抗生素更敏感。tmRNA标签的修饰和更高分辨率质谱方法的使用使得能够鉴定大量的天然tmRNA底物。特别重要的是理解的反式翻译的机制，我们报告的发现，一个扩展的tmRNA标签和广泛的梯状模式的内源性蛋白质标签事件在F。土拉菌，这可能是真细菌中tmRNA活性的普遍特征。此外，tmRNA标签的结构完整性和蛋白水解功能对于F.土拉热。重要的是，F.土拉菌在巨噬细胞内的复制受损，并且在土拉菌血症的小鼠模型中是无毒的。通过利用这些减毒表型，我们发现突变株提供有效的免疫保护，在小鼠对致命的皮内，腹膜，鼻内的挑战与完全毒力的亲本菌株。
Through targeted inactivation of the ssrA and smpB genes, we establish that the trans-translation process is necessary for normal growth, adaptation to cellular stress, and virulence by the bacterial pathogen Francisella tularensis. The mutant bacteria grow slower, have reduced resistance to heat and cold shocks, and are more sensitive to oxidative stress and sub-lethal concentrations of antibiotics. Modifications of the tmRNA tag and use of higher resolution mass spectrometry approaches enabled the identification of a large number of native tmRNA substrates. Of particular significance to understanding the mechanism of trans-translation, we report the discovery of an extended tmRNA tag and extensive ladder-like pattern of endogenous protein tagging events in F. tularensis that are likely to be a universal feature of tmRNA activity in eubacteria. Furthermore, the structural integrity and the proteolytic function of the tmRNA tag are both crucial for normal growth and virulence of F. tularensis. Significantly, trans-translation mutants of F. tularensis are impaired in replication within macrophages and are avirulent in mouse models of tularemia. By exploiting these attenuated phenotypes, we find that the mutant strains provide effective immune protection in mice against lethal intradermal, peritoneal, and intranasal challenges with the fully virulent parental strain.
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影响因子：
3.1
作者：
Golovliov, I;Baranov, V;Sjöstedt, A
通讯作者：
Sjöstedt, A
影响因子：
10.5
作者：
Gottesman, S;Roche, E;Sauer, RT
通讯作者：
Sauer, RT
影响因子：
11.4
作者：
Inada, T;Aiba, H
通讯作者：
Aiba, H
影响因子：
3.6
作者：
Abe, Teppei;Sakaki, Kazutaka;Muto, Akira
通讯作者：
Muto, Akira
DOI：
10.1073/pnas.0601838103
发表时间：
2006-09-26
影响因子：
11.1
作者：
Checroun, Claire;Wehrly, Tara D.;Celli, Jean
通讯作者：
Celli, Jean