Adhesin competence repressor (AdcR) from Streptococcus pyogenes controls adaptive responses to zinc limitation and contributes to virulence.
Adhesin competence repressor (AdcR) from Streptococcus pyogenes controls adaptive responses to zinc limitation and contributes to virulence.
复制标题
化脓性链球菌的粘附素能力阻遏物 (AdcR) 控制着对锌限制的适应性反应并有助于毒力。
DOI：
10.1093/nar/gku1304
复制
发表时间：
2015
影响因子：
14.9
通讯作者：
Kumaraswami,Muthiah
中科院分区：
文献类型：
--
作者：
Sanson,Misu;Makthal,Nishanth;Flores,AnthonyR;Olsen,RandallJ;Musser,JamesM;Kumaraswami,Muthiah
改变锌对细菌病原体的生物利用度是宿主先天免疫的关键组成部分。因此，感知和适应锌浓度变化的能力对于细菌的存活和发病至关重要。为了了解组astreplatin（GAS）的适应性反应，锌限制和其调节的AdcR，我们的特点是基因调控的AdcR。AdcR调节70个与锌获得和毒力有关的基因的表达。锌结合的AdcR与负调控启动子中的操纵子序列相互作用，并介导靶基因对锌缺乏的差异调节。参与锌动员和保护的基因在轻度缺锌期间被去抑制，而能量依赖性锌进口商在严重缺锌期间被上调。此外，我们证明了AdcR的转录激活通过直接结合启动子而发生。然而，AdcR的抑制和激活是由其与两个不同的操纵子序列的相互作用介导的。最后，AdcR的金属配体的突变分析导致DNA结合受损和毒力减弱，表明AdcR的锌传感对GAS发病至关重要。总之，我们证明了AdcR调节GAS对锌限制的适应性反应，并确定了缺锌期间GAS存活所需的分子组分。
Altering zinc bioavailability to bacterial pathogens is a key component of host innate immunity. Thus, the ability to sense and adapt to the alterations in zinc concentrations is critical for bacterial survival and pathogenesis. To understand the adaptive responses of group AStreptococcus(GAS) to zinc limitation and its regulation by AdcR, we characterized gene regulation by AdcR. AdcR regulates the expression of 70 genes involved in zinc acquisition and virulence. Zinc-bound AdcR interacts with operator sequences in the negatively regulated promoters and mediates differential regulation of target genes in response to zinc deficiency. Genes involved in zinc mobilization and conservation are derepressed during mild zinc deficiency, whereas the energy-dependent zinc importers are upregulated during severe zinc deficiency. Further, we demonstrated that transcription activation by AdcR occurs by direct binding to the promoter. However, the repression and activation by AdcR is mediated by its interactions with two distinct operator sequences. Finally, mutational analysis of the metal ligands of AdcR caused impaired DNA binding and attenuated virulence, indicating that zinc sensing by AdcR is critical for GAS pathogenesis. Together, we demonstrate that AdcR regulates GAS adaptive responses to zinc limitation and identify molecular components required for GAS survival during zinc deficiency.