Non-lethal control of the cariogenic potential of an agent-based model for dental plaque.

David A Head,Deirdre A Devine,Phil D Marsh

doi:10.1371/journal.pone.0105012

Abstract

Dental caries or tooth decay is a prevalent global disease whose causative agent is the oral biofilm known as plaque. According to the ecological plaque hypothesis, this biofilm becomes pathogenic when external challenges drive it towards a state with a high proportion of acid-producing bacteria. Determining which factors control biofilm composition is therefore desirable when developing novel clinical treatments to combat caries, but is also challenging due to the system complexity and the existence of multiple bacterial species performing similar functions. Here we employ agent-based mathematical modelling to simulate a biofilm consisting of two competing, distinct types of bacterial populations, each parameterised by their nutrient uptake and aciduricity, periodically subjected to an acid challenge resulting from the metabolism of dietary carbohydrates. It was found that one population was progressively eliminated from the system to give either a benign or a pathogenic biofilm, with a tipping point between these two fates depending on a multiplicity of factors relating to microbial physiology and biofilm geometry. Parameter sensitivity was quantified by individually varying the model parameters against putative experimental measures, suggesting non-lethal interventions that can favourably modulate biofilm composition. We discuss how the same parameter sensitivity data can be used to guide the design of validation experiments, and argue for the benefits of in silico modelling in providing an additional predictive capability upstream from in vitro experiments.

Highlights

Dental caries is a common disease that reduces quality of life globally and represents a substantial economic burden for health organisations [1]. It is caused by acids in the oral cavity which initiate demineralisation of tooth enamel, resulting in lesions that can develop into cavities. These acids are produced as a by-product of the glycolysis of dietary sugars by the bacterial community that comprises the oral biofilm known as dental plaque
The aim of this paper is to describe findings from an agent based model of supragingival plaque, i.e. that component of the oral biofilm above the gumline that is responsible for dental caries, developed to probe the relationship between evolving biofilm composition and cariogenic potential
Even for the early time point there is visible aggregation of each distinct population compared to the initial condition, and these aggregates evolve into the depth-spanning domains visible at the later time

Summary

Introduction

Dental caries is a common disease that reduces quality of life globally and represents a substantial economic burden for health organisations [1] It is caused by acids (primarily lactic) in the oral cavity which initiate demineralisation of tooth enamel, resulting in lesions that can develop into cavities. It is instead thought that any acid-producing species that can metabolise sugars at low pH, i.e. those that are both acidogenic and aciduric, can contribute to the caries process. This description includes S. mutans, and other mutans streptococci, lactobacilli, bifidobacteria, and others. Clinical trials have confirmed the correlation between biofilm composition and caries progression, with healthy and diseased sites associated with distinct subpopulations of bacteria [3,4,5]

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