Abstract

Dental caries occurs as a result of dysbiosis among commensal and pathogenic bacteria leading to demineralization of enamel within a dental biofilm (plaque) as a consequence of lower pH in the oral cavity. In our previous study, we have reported 1,3-disubstituted ureas particularly, 1,3-di-m-tolylurea (DMTU) could inhibit the biofilm formation along with lower concentrations of fluoride (31.25 ppm) without affecting bacterial growth. In the present study, RT-qPCR analysis showed the target specific molecular mechanism of DMTU. In vivo treatment with DMTU, alone or in combination with fluoride, resulted in inhibition of caries (biofilm development of Streptococcus mutans) using a Wistar rat model for dental caries. The histopathological analysis reported the development of lesions on dentine in infected subjects whereas the dentines of treated rodents were found to be intact and healthy. Reduction in inflammatory markers in rodents' blood and liver samples was observed when treated with DMTU. Collectively, data speculate that DMTU is an effective anti-biofilm and anti-inflammatory agent, which may improve the cariostatic properties of fluoride.

Highlights

  • Streptococcus mutans is known as one of the principal aetiological agent that plays a significant role in the transition of non-pathogenic commensal oral microbiota to highly acidic and cariogenic biofilms resulting in the development of dental caries

  • In S. mutans, biofilm formation is regulated by quorum sensing (QS) that involves ComDE twocomponent signal transduction system (TCSTS) which regulates the expression of virulence factors in cell density dependent manner

  • Our study examined the effects of DMTU and fluoride at mid-logarithmic growth phase and stationary growth phase

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Summary

Introduction

Streptococcus mutans is known as one of the principal aetiological agent that plays a significant role in the transition of non-pathogenic commensal oral microbiota to highly acidic and cariogenic biofilms resulting in the development of dental caries. Dental caries is one of the most common biofilm-dependent oral infectious diseases. The major virulence factors include acidogenicity and aciduricity along with its characteristic ability to produce dental plaque (biofilm). In S. mutans, biofilm formation is regulated by quorum sensing (QS) that involves ComDE twocomponent signal transduction system (TCSTS) which regulates the expression of virulence factors in cell density dependent manner. Secreted peptide is detected by the histidine kinase membrane-bound protein receptor, ComD, resulting in phosphorylation of its cytoplasmic response regulator, ComE

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