Ruxin Talia R, Schwartzman Julia A, Davidowitz Cleo R, Peters Zachary, Holtz Andrew, Haney Robet A, Spatafora Grace A
Department of Biology, Middlebury College, Middlebury, Vermont, USA.
Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Massachusetts, USA.
J Bacteriol. 2021 Jun 1;203(11). doi: 10.1128/JB.00678-20. Epub 2021 Mar 22.
is a commensal of the human oral microbiome that can promote dental caries under conditions of dysbiosis. This study investigates metalloregulators and their involvement in the oxidative stress response. Oxidative stress in the human mouth can derive from temporal increases in reactive oxygen species (ROS) after meal consumption and from endogenous bacterial ROS-producers that colonize the dentition. We hypothesize that the PerR (SMU.593) and SloR (SMU.186) metalloregulatory proteins contribute to the regulation of oxidative stress genes and their products. Expression assays with UA159 wild type cultures exposed to HO reveal that HO upregulates , and that PerR represses transcription upon binding directly to Fur and PerR consensus sequences within the operator. In addition, the results of Western blot experiments implicate the Clp proteolytic system in SloR degradation under conditions of HO-stress. To reveal a potential role for SloR in the HO-resistant phenotype of GMS802 (a -deficient strain), we generated a / double knockout mutant, GMS1386, where we observed upregulation of the and antioxidant genes. These results are consistent with GMS802 HO resistance and with a role for PerR as a transcriptional repressor. Cumulatively, these findings support a reciprocal relationship between PerR and SloR during the oxidative stress response and begin to elucidate the fitness strategies that evolved to foster persistence in the transient environments of the human oral cavity.In 2020, untreated dental caries, especially in the permanent dentition, ranked among the most prevalent infectious diseases worldwide, disproportionately impacting individuals of low socioeconomic status. Untreated caries can lead to systemic health problems and has been associated with extended school and work absences, inappropriate use of emergency departments, and an inability for military forces to deploy. Together with public health policy, research aimed at alleviating induced tooth decay is important because it can improve oral health (and overall health), especially in underserved populations. This research, focused on metalloregulatory proteins and their gene targets, is significant because it can promote virulence gene control in an important oral pathogen, and contribute to the development of an anti-caries therapeutic that can reduce tooth decay.
是人类口腔微生物群的共生菌，在生态失调的情况下可促进龋齿。本研究调查金属调节因子及其在氧化应激反应中的作用。人类口腔中的氧化应激可源于进食后活性氧（ROS）的短暂增加以及定殖于牙列的内源性细菌ROS产生菌。我们假设PerR（SMU.593）和SloR（SMU.186）金属调节蛋白有助于调节氧化应激基因及其产物。用暴露于HO的UA159野生型培养物进行的表达分析表明，HO上调，并且PerR在直接结合到操纵子内的Fur和PerR共有序列后抑制转录。此外，蛋白质印迹实验结果表明，在HO应激条件下，Clp蛋白水解系统参与SloR的降解。为了揭示SloR在GMS802（一种α缺陷菌株）的HO抗性表型中的潜在作用，我们构建了一个/双敲除突变体GMS1386，在其中我们观察到和抗氧化基因的上调。这些结果与GMS802的HO抗性以及PerR作为转录阻遏物的作用一致。累积起来，这些发现支持了PerR和SloR在氧化应激反应期间的相互关系，并开始阐明为促进在人类口腔短暂环境中的持久性而进化出的适应性策略。2020年，未经治疗的龋齿，尤其是恒牙龋齿，是全球最普遍的传染病之一，对社会经济地位较低的个体影响尤为严重。未经治疗的龋齿可导致全身健康问题，并与长期缺课、工作缺勤、不适当使用急诊科以及军队无法部署有关。与公共卫生政策一起，旨在减轻所致龋齿的研究很重要，因为它可以改善口腔健康（以及整体健康），尤其是在服务不足的人群中。这项专注于金属调节蛋白及其基因靶点的研究很重要，因为它可以促进对一种重要口腔病原体中毒力基因的控制，并有助于开发一种可以减少龋齿的抗龋治疗方法。
