RegA, the Regulator of the Two-Component System RegB/RegA of Brucella suis, Is a Controller of Both Oxidative Respiration and Denitrification Required for Chronic Infection in Mice

RegA, the Regulator of the Two-Component System RegB/RegA of Brucella suis, Is a Controller of Both Oxidative Respiration and Denitrification Required for Chronic Infection in Mice
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DOI:
10.1128/iai.00063-13
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发表时间:
2013-06-01
影响因子:
3.1
通讯作者:
Jubier-Maurin, Veronique
Jubier-Maurin, Veronique
中科院分区:
医学2区
文献类型:
--
作者:
Abdou, Elias;Deredjian, Amelie;Jubier-Maurin, Veronique

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对缺氧的适应对于布鲁氏菌在宿主体内的毒力和持久性是至关重要的。这种细菌在缺氧方面的灵活性是显著的,因为猪种布鲁氏菌可以使用FnrN家族的一个氧依赖的转录调节因子,两个高亲和力的氧末端氧化酶和一个完整的反硝化途径来抵抗各种缺氧条件。此外,我们以前的研究结果表明,在微好氧条件下,猪芽孢杆菌可以同时利用氧化呼吸和反硝化作用。亚硝酸还原酶的表达需要一个具有功能的细胞色素BD泛喹酚氧化酶,这证明了这两条途径的联系,并证明了RegB/RegA双组分系统在两个呼吸系统的协调控制中的中心作用。我们提出了一种通过转录调节因子RegA对猪链霉菌呼吸途径进行全球调控的方案,该方案假定细胞色素BD泛喹酚氧化酶在氧化还原信号传递到组氨酸传感器激酶RegB中发挥作用。更重要的是,研究发现,RegA对于猪芽胞杆菌在体内氧气限制靶器官内的持续存在是必不可少的。可以想象,RegA在布鲁氏菌慢性感染的特征--持久状态的建立中,扮演着许多系统的控制器的角色。
Adaptation to oxygen deficiency is essential for virulence and persistence of Brucella inside the host. The flexibility of this bacterium with respect to oxygen depletion is remarkable, since Brucella suis can use an oxygen-dependent transcriptional regulator of the FnrN family, two high-oxygen-affinity terminal oxidases, and a complete denitrification pathway to resist various conditions of oxygen deficiency. Moreover, our previous results suggested that oxidative respiration and denitrification can be simultaneously used by B. suis under microaerobiosis. The requirement of a functional cytochrome bd ubiquinol oxidase for nitrite reductase expression evidenced the linkage of these two pathways, and the central role of the two-component system RegB/RegA in the coordinated control of both respiratory systems was demonstrated. We propose a scheme for global regulation of B. suis respiratory pathways by the transcriptional regulator RegA, which postulates a role for the cytochrome bd ubiquinol oxidase in redox signal transmission to the histidine sensor kinase RegB. More importantly, RegA was found to be essential for B. suis persistence in vivo within oxygen-limited target organs. It is conceivable that RegA acts as a controller of numerous systems involved in the establishment of the persistent state, characteristic of chronic infections by Brucella.