Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 9 August 2020 / Approved: 11 August 2020 / Online: 11 August 2020 (08:11:20 CEST)

How to cite: Kalimuthu, S.; Cheung, B.P.; Yau, J.Y.; Shanmugam, K.; Solomon, A.P.; Neelakantan, P. A Novel Small Molecule, 1,3-di-m-tolyl-urea, Inhibits and Disrupts Multispecies Oral Biofilms. Preprints 2020, 2020080259 (doi: 10.20944/preprints202008.0259.v1). Kalimuthu, S.; Cheung, B.P.; Yau, J.Y.; Shanmugam, K.; Solomon, A.P.; Neelakantan, P. A Novel Small Molecule, 1,3-di-m-tolyl-urea, Inhibits and Disrupts Multispecies Oral Biofilms. Preprints 2020, 2020080259 (doi: 10.20944/preprints202008.0259.v1).

Abstract

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 mutansbiofilms 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, 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 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.

Subject Areas

DMTU; Multispecies biofilms; Porphyromonas gingivalis; Quorum sensing

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