In vitro manganese-dependent cross-talk between Streptococcus mutans VicK and GcrR: implications for overlapping stress response pathways.
In vitro manganese-dependent cross-talk between Streptococcus mutans VicK and GcrR: implications for overlapping stress response pathways.
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DOI：
10.1371/journal.pone.0115975
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Goodman SD
中科院分区：
文献类型：
--
作者：
Downey JS;Mashburn-Warren L;Ayala EA;Senadheera DB;Hendrickson WK;McCall LW;Sweet JG;Cvitkovitch DG;Spatafora GA;Goodman SD
变形链球菌是牙菌斑生物膜的主要产酸成分，在龋病病因学中起着关键作用。以前，我们证明了VicRK双组分信号转导系统调节生物膜的形成，氧化应激和耐酸性反应在S。变异人使用体外磷酸化测定，在这里，我们证明了第一次，除了激活其同源的反应调节蛋白，传感器激酶，VicK可以transphosphorylate的非同源应激调节反应调节，GcrR，在锰的存在下。锰是一种重要的微量营养素，以前曾被认为与龋齿发病率相关，并且是链球菌SloR介导的金属调节的效应子。变异体我们的研究结果支持锰对VicRK，GcrR和SloR的调节作用，以及由这些组分形成的交叉调节网络比以前认识到的更复杂。使用DNaseI足迹法，我们观察到重叠的DNA结合特异性VicR和GcrR在天然启动子，这些蛋白质是相同的转录调节子的一部分。我们的研究结果也支持的作用，SloR作为一个积极的调节vicRK两个组件的信号系统，因为它的转录在SloR缺陷突变体大幅减少。这些发现证明了在S.变形菌锰依赖性反应，涉及非同源信号转导系统（VicRK和GcrR）之间的串扰，以调节应激反应途径。
Streptococcus mutans, a major acidogenic component of the dental plaque biofilm, has a key role in caries etiology. Previously, we demonstrated that the VicRK two-component signal transduction system modulates biofilm formation, oxidative stress and acid tolerance responses in S. mutans. Using in vitro phosphorylation assays, here we demonstrate for the first time, that in addition to activating its cognate response regulator protein, the sensor kinase, VicK can transphosphorylate a non-cognate stress regulatory response regulator, GcrR, in the presence of manganese. Manganese is an important micronutrient that has been previously correlated with caries incidence, and which serves as an effector of SloR-mediated metalloregulation in S. mutans. Our findings supporting regulatory effects of manganese on the VicRK, GcrR and SloR, and the cross-regulatory networks formed by these components are more complex than previously appreciated. Using DNaseI footprinting we observed overlapping DNA binding specificities for VicR and GcrR in native promoters, consistent with these proteins being part of the same transcriptional regulon. Our results also support a role for SloR as a positive regulator of the vicRK two component signaling system, since its transcription was drastically reduced in a SloR-deficient mutant. These findings demonstrate the regulatory complexities observed with the S. mutans manganese-dependent response, which involves cross-talk between non-cognate signal transduction systems (VicRK and GcrR) to modulate stress response pathways.
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影响因子：
3.6
作者：
Anjem A;Varghese S;Imlay JA
通讯作者：
Imlay JA
影响因子：
3.7
作者：
Dmitriev A;Mohapatra SS;Chong P;Neely M;Biswas S;Biswas I
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影响因子：
3.6
作者：
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Msadek, Tarek
影响因子：
3.1
作者：
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通讯作者：
Mattos-Graner, Renata O.
影响因子：
3.2
作者：
Biswas, S;Biswas, I
通讯作者：
Biswas, I