Bacteriophages in dental caries: Roles and potential as a therapy - PROJECT SUMMARY / ABSTRACT Bacteriophages (phages), or viruses that infect bacteria, are key drivers of ecological fluctuations within microbial communities and can have broad impacts on bacterial abundances and behaviors. With recent advances in ecogenomics from metagenomic/metatranscriptomic sequencing as well as computational approaches, an eco-systems biology approach has been developed to interrogate the role of phages in different environments: from the oceans and soils to human-related microbiomes such as the gut. Over the last decade, a handful of studies have explored phage in the human oral microbiome in the context of health and periodontal disease. However, there has been no robust study of phage (their abundance, characteristics or their gene products) during the dysbiotic microbial events that lead up to the formation of dental caries. This Katz R01 proposal from a multi-PI team featuring a clinical pediatric dentist and basic science microbiologist aims to leverage a phage-specific computational platform built up from studying the impact of viruses in our earth’s oceans into defining the role of phage in dental caries and the broader oral microbiome. Within Aim 1, the composition, abundance and role of the oral phageome in early childhood caries (ECC) will be explored through the collection of caries-free and caries-active plaque samples, DNA/RNA sequencing of total and/or virulent phage populations, and utilization of the iVirus 2.0 toolkit for sequencing analysis. Results from this aim will describe key phage taxa and accessory genes that are contributors to previously described shifts in bacterial population structures during the transition from health to disease. In addition, there has been renewed interest in phage for use as a therapeutic approach (i.e., phage therapy) to kill select bacterial pathogens. Since 2020, 50 different clinical trials have been initiated, either observational or interventional, involving phages. None of these involved the oral cavity. We propose within Aim 2 to isolate and characterize phages against a panel of cariogenic organisms including Streptococcus mutans to develop phages cocktails and combination therapies for in vitro testing. This includes establishment of the first U.S.-based oral phage bank, testing of specific phage cocktails on multi-species biofilms, and beginning to define how oral bacteria respond to phage infection (both target and non-target species). In all, the summation of this project begins to shed light on the role of phage and their potential as an intervention strategy in dental caries and represents a change in research direction for both principal investigators. Advances here will integrate phage into our broader understanding of the oral microbial ecosystem, providing a sustainable research direction for two early career investigators in oral microbiology.
