Abstract

An imbalance of homeostasis between the microbial communities and the host system leads to dysbiosis in oral micro flora. DMTU (1,3-di-m-tolyl-urea) is a biocompatible compound that was shown to inhibit Streptococcus mutans biofilm by inhibiting its communication system (quorum sensing). Here, we hypothesized that DMTU is able to inhibit multispecies biofilms. We developed a multispecies oral biofilm model, comprising an early colonizer Streptococcus gordonii, a bridge colonizer Fusobacterium nucleatum, and late colonizers Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. We performed comprehensive investigations to demonstrate the effect of DMTU on planktonic cells and biofilms. Our findings showed that DMTU inhibits and disrupts multispecies biofilms without bactericidal effects. Mechanistic studies revealed a significant down regulation of biofilm and virulence-related genes in P. gingivalis. Taken together, our study highlights the potential of DMTU to inhibit polymicrobial biofilm communities and their virulence.

Highlights

  • Microbial communities exist in homeostasis with the host in healthy individuals

  • Macrophage polarization M1/M2 is maintained as a response to chronic inflammatory responses, but studies have shown that patients with periodontitis show reduced macrophage polarization, eventually affecting the host immune surveillance [13]

  • Our results revealed that DMTU inhibits multispecies biofilm development and disrupts preformed biofilms without any effect on bacterial viability

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Summary

Introduction

Microbial communities exist in homeostasis with the host in healthy individuals. factors including epigenetic and genetic changes, and stress conditions such as smoking and systemic diseases, trigger an imbalance in this homeostasis by creating dysbiosis within microbial communities [1,2]. P. gingivalis plays an important role in tissue breakdown by modulating the host immune response and invading epithelial cells via the production of several proteases (gingipains) [10] This results in the release of collagen and heme, which are used as nutritional sources for further growth and biofilm development [1,11]. Animal studies have demonstrated that P. gingivalis alone is incapable of causing virulence in germ-free mice [14] These findings suggest that oral dysbiosis, due to the interplay and cross-talk between P. gingivalis and other oral organisms, plays a significant role in modulating the host immune response [12,13]. Our results revealed that DMTU inhibits multispecies biofilm development and disrupts preformed biofilms without any effect on bacterial viability

Materials and Methods
Effect of DMTU on Bacterial Growth
Co-Culture and Biofilm Formation
Biofilm Inhibition by Sub-Inhibitory Concentrations of DMTU
Effects of DMTU on Preformed Biofilms
Biofilm Inhibition on DMTU-Coated Substrates
Effect of DMTU on Preformed Biofilms
Statistical Analysis
Results and Discussion
Full Text
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