SloR-SRE 与 S. mutans mntH 启动子的结合是合作性的。

IF 2.7 3区 生物学 Q3 MICROBIOLOGY
Journal of Bacteriology Pub Date : 2025-05-22 Epub Date: 2025-03-31 DOI:10.1128/jb.00470-24
Myrto Ziogas, India Drummond, Igor Todorovic, Katie Kraczkowsky, Yiran Han, Hua Zhang, Hui Wu, Grace Spatafora
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引用次数: 0

摘要

变形链球菌是菌斑微生物群的共栖成员。当膳食糖可用于变形链球菌发酵时,这种情况尤其普遍,产生酸副产物,降低菌斑pH值,促进蛀牙。变形链球菌可以在短暂的口腔环境中存活,部分原因是它可以在有金属离子的盛宴期间调节锰和铁的吸收,而在金属离子有限的饥荒期间调节锰和铁的吸收。变形链球菌依赖于一种25kDa的金属调节蛋白,称为SloR,来调节细菌细胞表面对这些阳离子的吸收。当与锰结合时,SloR结合在变形链球菌中编码主要锰转运体的sloABC基因启动子中的回文识别元件上。文献报道描述了变形链球菌中的辅助锰转运体MntH,它也受SloR控制。在本研究中,我们进行了表达谱实验,揭示了sloABC和mntH基因在转录水平上的协调调节。此外,我们描述了mntH基因产物的作用,与sloabc编码的金属离子摄取机制是冗余的。dna结合研究的结果支持SloR直接结合到mntH启动子区域,该区域与sloABC启动子区域一样,包含三个回文识别元件,SloR与这些元件协同结合以抑制下游转录。这些发现扩大了我们对SloR金属调控的理解,并阐明了SloR- dna结合对变形链球菌口腔金属离子稳态和适应性至关重要。重要性:在美国和国外,龋齿不成比例地影响低收入社会经济群体。变异链球菌是人类龋齿的主要病原体,其研究对减轻或预防龋齿具有重要意义。SloR蛋白是由sloABC-和mntH基因编码的S. mutans金属离子摄取机制的主要调节因子。这种slor介导的基因控制对于维持细胞内金属离子稳态至关重要,因此变形链球菌在斑块微生物群中的适应性也很重要。更好地了解sloABC和mntH金属离子转运体及其在SloR中的调控作用,可以指导合理的药物设计,通过靶向SloR- dna结合界面,减轻或预防变形链球菌诱导的疾病。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
SloR-SRE binding to the S. mutans mntH promoter is cooperative.

Streptococcus mutans is a commensal member of the plaque microbiome. It is especially prevalent when dietary sugars are available for S. mutans fermentation, generating acid byproducts that lower plaque pH and foster tooth decay. S. mutans can survive in the transient conditions of the mouth, in part because it can regulate the uptake of manganese and iron during periods of feast when metal ions are available, and famine when they are limited. S. mutans depends on a 25kDa metalloregulatory protein, called SloR, to modulate the uptake of these cations across the bacterial cell surface. When bound to manganese, SloR binds to palindromic recognition elements in the promoter of the sloABC genes that encode the major manganese transporter in S. mutans. Reports in the literature describe MntH, an ancillary manganese transporter in S. mutans, that is also subject to SloR control. In the present study, we performed expression profiling experiments that reveal coordinate regulation of the sloABC and mntH genes at the level of transcription. In addition, we describe a role for the mntH gene product that is redundant with that of the sloABC-encoded metal ion uptake machinery. The results of DNA-binding studies support direct SloR binding to the mntH promoter region which, like that at the sloABC promoter, harbors three palindromic recognition elements to which SloR binds cooperatively to repress downstream transcription. These findings expand our understanding of the SloR metalloregulome and elucidate SloR-DNA binding that is essential for S. mutans metal ion homeostasis and fitness in the oral cavity.

Importance: Dental caries disproportionately impacts low-income socioeconomic groups in the United States and abroad. Research that is focused on S. mutans, the primary causative agent of dental caries in humans, is significant to mitigation efforts aimed at alleviating or preventing dental caries. The SloR protein is a major regulator of the S. mutans metal ion uptake machinery encoded by the sloABC- and mntH genes. This SloR-mediated gene control is essential for maintaining intracellular metal ion homeostasis, and hence S. mutans fitness in the plaque microbiome. An improved understanding of the sloABC and mntH metal ion transporters and their regulation by SloR can guide rational drug design that, by targeting the SloR-DNA-binding interface, can alleviate or prevent S. mutans-induced disease.

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来源期刊
Journal of Bacteriology
Journal of Bacteriology 生物-微生物学
CiteScore
6.10
自引率
9.40%
发文量
324
审稿时长
1.3 months
期刊介绍: The Journal of Bacteriology (JB) publishes research articles that probe fundamental processes in bacteria, archaea and their viruses, and the molecular mechanisms by which they interact with each other and with their hosts and their environments.
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