The role of bacterial communication in the shift from disease to health in the oral cavity

Background
The human oral cavity harbours over 900 different bacterial phylotypes. A delicately
balanced symbiosis between oral microbes and host immune-inflammatory cells ensures a
healthy and stable oral environment. Changes in this balance can lead to dysbiosis and
disease, and recent data supports an intimate relationship between the oral biofilm and
host response, whereby inflammation drives dysbiosis and vice versa.
The ecological plaque hypothesis proposes that physiological and environmental factors are
important in the regulation or dysregulation of oral health and in particular the
development of the dental plaque biofilm.
Microorganisms within the oral biofilm (plaque) co-aggregate and interact with each other
in an organised fashion. It has long been known that bacteria communicate within their own
species, but also across species and also with eukaryotic cells. However, this communication
and its role and importance in virulence factor expression, disease progression, biofilm
formation and maturation in the oral cavity is still poorly understood. In particular quorum
sensing, a form of bacterial cell-cell communication, dependent on cell density, requires
further investigation. It has been shown elsewhere that interruption of quorum sensing
circuits, can be used to reduce pathogenicity and could constitute future disease treatment
and prevention strategies.

Hypothesis
Interbacterial communication (quorum sensing) contributes to the establishment and
maintenance of a disease-associated plaque biofilm.

Objectives/Methods
Part 1: Genomics
- Analysis of the genomes of defined Periodontal pathogens in search of quorum sensing
genes, other forms of communication, such as cyclic di AMP and GMP
Part 2: Molecular Microbiology
- Create mutants (knockouts) in Porphyromonas gingivalis and Fusobacterium nucleatum
to disrupt quorum sensing pathways
- Characterise mutants (pathogenicity, biofilm formation, co-aggregation, interaction
with eukaryotic cells)
- Determine quorum sensing molecules (based on genomics or also metabolomics data -
which are already accessible); attempt to purify, characterise (test addition of these
molecules to cultures)
Part 3: Models
- Models of plaque: mono to multi-species biofilms, static, in flow
o Incorporating mutants and/or QS molecules
- Cell-bacterial models, including hydrogels with keratinocytes, neutrophils and
fibroblasts
o Test influence on eukaryotic cells
o QS blockers, treatments?
Part 4: Application
- Detection of QS molecules in plaque, GCF or Saliva in health and disease states:
indicator of disease
- QS blockers to reduce dental plaque?

Expected Outcomes
- Potential for novel detection methods of Periodontal risk and disease status
- Potential for new treatment methods for Periodontal and other oral diseases
- New models to study bacterial and host interactions, in particular communication, to be
used to understand impact of existing and new treatment approaches.