The stringent response mediator Rsh is required for Brucella melitensis and Brucella suis virulence, and for expression of the type IV secretion system virB
The stringent response mediator Rsh is required for Brucella melitensis and Brucella suis virulence, and for expression of the type IV secretion system virB
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DOI：
10.1111/j.1462-5822.2006.00749.x
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发表时间：
2006-11-01
影响因子：
3.4
通讯作者：
Kohler, Stephan
中科院分区：
文献类型：
--
作者：
Dozot, Marie;Boigegrain, Rose-Anne;Kohler, Stephan
细胞内细菌的生理适应对于与真核宿主细胞及时相互作用至关重要。一种适应机制，即严格反应，是由营养胁迫通过其效应分子（p）ppGpp诱导的，该效应分子由RelA/SpoT同源物的作用合成。胞内病原体布鲁氏菌，布鲁氏菌病的病原体，具有与relA/spoT同源的基因，命名为rsh，编码（p）ppGpp合成酶，如通过苜蓿中华根瘤菌的relA突变体的异源互补所证实的。猪种布鲁氏菌和羊种布鲁氏菌中的Rsh缺失突变体的特征在于改变的形态，以及在饥饿条件下以及在细胞和小鼠感染模型中的存活率降低。最有趣的是，我们证明了编码IV型分泌系统（布鲁氏菌的主要毒力因子）的virB的表达是Rsh依赖的。所有突变表型（包括缺乏VirB蛋白）都与布氏杆菌的rsh基因互补。此外，S.苜蓿草在功能上取代了布鲁氏菌Rsh，描述了来自植物共生体的基因在哺乳动物病原体中恢复毒力的能力。因此，我们的结论是，在巨噬细胞内的环境中遇到的布鲁氏菌，RSH可能参与了适应的病原体低营养环境，并间接在VirB介导的最终复制生态位的形成。
Physiological adaptation of intracellular bacteria is critical for timely interaction with eukaryotic host cells. One mechanism of adaptation, the stringent response, is induced by nutrient stress via its effector molecule (p)ppGpp, synthesized by the action of RelA/SpoT homologues. The intracellular pathogen Brucella spp., causative agent of brucellosis, possesses a gene homologous to relA/spoT, named rsh, encoding a (p)ppGpp synthetase as confirmed by heterologous complementation of a relA mutant of Sinorhizobium meliloti. The Rsh deletion mutants in Brucella suis and Brucella melitensis were characterized by altered morphology, and by reduced survival under starvation conditions and in cellular and murine models of infection. Most interestingly, we evidenced that expression of virB, encoding the type IV secretion system, a major virulence factor of Brucella, was Rsh-dependent. All mutant phenotypes, including lack of VirB proteins, were complemented with the rsh gene of Brucella. In addition, RelA of S. meliloti functionally replaced Brucella Rsh, describing the capacity of a gene from a plant symbiont to restore virulence in a mammalian pathogen. We therefore concluded that in the intramacrophagic environment encountered by Brucella, Rsh might participate in the adaptation of the pathogen to low-nutrient environments, and indirectly in the VirB-mediated formation of the final replicative niche.