Abstract

Oral microbial dysbiosis is the major causative factor for common oral infectious diseases including dental caries and periodontal diseases. Interventions that can lessen the microbial virulence and reconstitute microbial ecology have drawn increasing attention in the development of novel therapeutics for oral diseases. Antimicrobial small molecules are a series of natural or synthetic bioactive compounds that have shown inhibitory effect on oral microbiota associated with oral infectious diseases. Novel small molecules, which can either selectively inhibit keystone microbes that drive dysbiosis of oral microbiota or inhibit the key virulence of the microbial community without necessarily killing the microbes, are promising for the ecological management of oral diseases. Here we discussed the research progress in the development of antimicrobial small molecules and delivery systems, with a particular focus on their antimicrobial activity against typical species associated with oral infectious diseases and the underlying mechanisms.

Highlights

  • The oral microbiota, including more than 700 microbial species, are the most complicated microbial communities in human body (Dewhirst et al, 2010)

  • Periodontitis is believed to be the consequence of a broadly-based dysbiotic alteration in periodontal microbiota, whereby some keystone species such as P. gingivalis triggers the development of this disease (Hajishengallis and Lamont, 2012)

  • The results showed that polysaccharide nanoparticles possessed enhanced antimicrobial activities as compared to pure curcumin

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Summary

INTRODUCTION

The oral microbiota, including more than 700 microbial species, are the most complicated microbial communities in human body (Dewhirst et al, 2010). According to the ecological plaque hypothesis, oral microbial dysbiosis leads to the occurrence of oral infectious diseases including dental caries and periodontal diseases, which seriously endanger oral and general health (Theilade, 1986). Drug screening from existing small-molecule libraries or natural resources, and target-based designing are most common approaches to the development of small molecules that target oral microbiota and benefit oral infectious disease control. We aimed to discuss the research progress in the development of antimicrobial small molecules and delivery systems, with a particular focus on: 1) their antimicrobial activity against keystone bacteria including S. mutans, P. gingivalis and C. albicans; 2) their inhibitory effects on the pheromones that mediate interspecies communications within polymicrobial communities; 3) the research progress in the development of delivery systems that enhance the antimicrobial activity of small molecules in the management of oral infectious diseases. SMALL MOLECULES THAT INHIBIT KEYSTONE BACTERIA ASSOCIATED WITH ORAL INFECTIOUS DISEASES

Streptococcus mutans
Antimicrobial activity
Ursolic acid
Selectively bond GtfC and significantly inhibit the biofilm formation
Porphyromonas gingivalis
Candida albicans
Synthetic molecules DANA
Natural Compounds Quercetin
Quantum curcumin
SMALL MOLECULES THAT INHIBIT QUORUM SENSING SYSTEM
Phenotypic screening from molecule libraries azoffluxin
Disulfiram ENOblock
NOVEL DRUG DELIVERY SYSTEMS OF ANTIMICROBIAL SMALL MOLECULES
Organic Polymers
Metallic Nanoparticles
Tetrahedral Framework Nucleic Acids
Findings
CONCLUSION
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