A Novel Small Molecule, 1,3-di-m-tolyl-urea, Inhibits and Disrupts Multispecies Oral Biofilms

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 inhibitStreptococcus mutansbiofilm 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 colonizerStreptococcus gordonii, a bridge colonizerFusobacterium nucleatum, and late colonizersPorphyromonas gingivalisandAggregatibacter 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 inP. gingivalis. Taken together, our study highlights the potential of DMTU to inhibit polymicrobial biofilm communities and their virulence.