Department of Biology, Middlebury College , Middlebury, Vermont, USA.
Department of Restorative Dentistry, School of Dentistry, Oregon Health and Science University , Portland, Oregon, USA.
J Bacteriol. 2023 Sep 26;205(9):e0017223. doi: 10.1128/jb.00172-23. Epub 2023 Sep 11.
Dental caries is among the most prevalent chronic diseases worldwide. , the chief causative agent of caries, uses a 25-kDa manganese-dependent SloR protein to coordinate the uptake of essential manganese with the transcription of its virulence attributes. Small non-coding RNAs (sRNAs) can either enhance or repress gene expression, and reports in the literature ascribe an emerging role for sRNAs in the environmental stress response. Herein, we focused our attention on 18-50 nt sRNAs as mediators of the SloR and manganese regulons. Specifically, the results of RNA sequencing revealed 19 sRNAs in which were differentially transcribed in the SloR-proficient UA159 and SloR-deficient GMS584 strains, and 10 sRNAs that were differentially expressed in UA159 cells grown in the presence of low vs high manganese. We describe SmsR1532 and SmsR1785 as SloR- and manganese-responsive sRNAs that are processed from large transcripts and that bind SloR directly in their promoter regions. The predicted targets of these sRNAs include regulators of metal ion transport, growth management via a toxin-antitoxin operon, and oxidative stress tolerance. These findings support a role for sRNAs in coordinating intracellular metal ion homeostasis with virulence gene control in an important oral cariogen. IMPORTANCE Small regulatory RNAs (sRNAs) are critical mediators of environmental signaling, particularly in bacterial cells under stress, but their role in is poorly understood. the principal causative agent of dental caries, uses a 25-kDa manganese-dependent protein, called SloR, to coordinate the regulated uptake of essential metal ions with the transcription of its virulence genes. In the present study, we identified and characterized sRNAs that are both SloR and manganese responsive. Taken together, this research can elucidate the details of regulatory networks that engage sRNAs in an important oral pathogen and that can enable the development of an effective anti-caries therapeutic.
龋齿是全球最普遍的慢性疾病之一。作为龋齿的主要病原体，使用一种 25kDa 的锰依赖型 SloR 蛋白来协调必需锰的摄取与毒力特性的转录。小非编码 RNA（sRNA）可以增强或抑制基因表达，文献中的报道赋予了 sRNA 在环境应激反应中的新兴作用。在此，我们将注意力集中在介导 SloR 和锰调控子的 18-50nt sRNA 上。具体而言，RNA 测序的结果显示，在 SloR 功能齐全的 UA159 和 SloR 缺失的 GMS584 菌株中，有 19 种 sRNA 差异转录，在低锰和高锰存在下生长的 UA159 细胞中，有 10 种 sRNA 差异表达。我们将 SmsR1532 和 SmsR1785 描述为 SloR 和锰反应性 sRNA，它们从大转录本中加工而来，并直接在其启动子区域结合 SloR。这些 sRNA 的预测靶标包括金属离子转运调节剂、通过毒素-抗毒素操纵子进行的生长管理，以及氧化应激耐受性。这些发现支持 sRNA 在协调细胞内金属离子稳态与重要口腔致龋菌毒力基因控制中的作用。重要性 小调控 RNA（sRNA）是环境信号的关键介质，特别是在应激状态下的细菌细胞中，但它们在 中的作用知之甚少。作为龋齿的主要病原体，使用一种 25kDa 的锰依赖型蛋白，称为 SloR，来协调必需金属离子的调节摄取与毒力基因的转录。在本研究中，我们鉴定并表征了既受 SloR 又受锰调控的 sRNA。总之，这项研究可以阐明参与重要口腔病原体的调控网络的细节，并能够开发出有效的抗龋齿治疗方法。
