Carbohydrate Metabolism Regulated by Antisense vicR RNA in Cariogenicity. (February 2020)

• Record Type: Journal Article
• Authors: Lei, L.; Zhang, B.; Mao, M.; Chen, H.; Wu, S.; Deng, Y.; Yang, Y.; Zhou, H.; Hu, T.
• Is Part Of: Journal of dental research. Volume 99:Number 2(2020)
• Page Start: 204
• Page End: 213
• Publication Date: 2020-02
• Subjects: Streptococcus mutans -- biofilm -- dental plaque -- noncoding RNA -- polysaccharides -- regulation; Dentistry -- Periodicals; Dentistry -- Social aspects -- Periodicals; Dentistry -- Periodicals; Research -- Periodicals; 617.6005
• DOI: 10.1177/0022034519890570
• Languages: English
• ISSNs: 0022-0345

Abstract

Streptococcus mutans is a major cariogenic pathogen that resides in multispecies oral microbial biofilms. The VicRK 2-component system is crucial for bacterial adaptation, virulence, and biofilm organization and contains a global and vital response regulator, VicR. Notably, we identified an antisense vicR RNA (AS vicR ) associated with an adjacent RNase III–encoding ( rnc ) gene that was relevant to microRNA-size small RNAs (msRNAs). Here, we report that ASvicR overexpression significantly impeded bacterial growth, biofilm exopolysaccharide synthesis, and cariogenicity in vivo. Transcriptome analysis revealed that the AS vicR RNA mainly regulated carbohydrate metabolism. In particular, overproducing AS vicR demonstrated a reduction in galactose and glucose metabolism by monosaccharide composition analysis. The results of high-performance gel permeation chromatography revealed that the water-insoluble glucans isolated from AS vicR presented much lower molecular weights. Furthermore, direct evidence showed that total RNAs were disrupted by rnc -encoded RNase III. With the coexpression of T4 RNA ligase, putative msRNA1657, which is an rnc -related messenger RNA, was verified to bind to the 5′-UTR regions of the vicR gene. Furthermore, AS vicR regulation revealed a sponge regulatory-mediated network for msRNA associated with adjacent RNase III–encoding genes. There was an increase in AS vicR transcript levels in clinical S. mutans strains from caries-free children, while the expression of AS vicR was decreased in early childhood caries patients; this outcome may be explored as a potential strategy contributing to the management of dental caries. Taken together, our findings suggest an important role of AS vicR -mediated sponge regulation in S. mutans, indicating the characterization of lactose metabolism by a vital response regulator in cariogenicity. These findings have a number of implications and have reshaped our understanding of bacterial gene regulation from its transcriptional conception to the key roles of regulatory RNAs.