Programme in Microbiology of the Oral Cavity

Dr R. A. Whiley, Dr R. P. Allaker

Current projects are:

Host pathogen interaction in the microenvironment and systemic disease - Dr. R.A. Whiley

This work focuses on the diversity of oral commensal bacteria and opportunist pathogens at the species and intra-species level with a focus on the oral streptococci and includes:

  • Research on the Anginosus species group (previously included within a single species, ‘Streptococcus milleri’) which has revealed the presence of three species with discernable clinical associations. One member species, Streptococcus intermedius, is the focus of current research and has been shown to be involved with deep-seated abscesses notably of the brain and liver.
  • Studies concerned with the expression by this species of a novel, human-specific, thiol-activated cytotoxin, called Intermedilysin, which is expressed only by strains of S. intermedius, but not by any close relative, and at higher levels in strains isolated from deep-seated infections compared with those from normal dental plaque and peripheral infection sites. Intermedilysin belongs to a family of pore-forming toxins that are able to cause target cell membrane disruption and cell death.

Studies on Intermedilysin, carried out in collaboration with Tokushima University, Japan, aim to understand the role of this cytotoxin in the formation of abscesses at deep-seated sites. The main focus within this area of work is to understand the effects of Intermedilysin on the viability and function of human target cells. These include neutrophils which predominate within the environment of the abscess and which this bacterium clearly has to contend with in-vivo as well as other cell types including primary brain endothelial cells (HBMEC), neuronal cell lines (DAOY and SH-SY5Y), astrocytes, liver cells (HepG2) as well as oral keratinocytes (TR146).  These studies demonstrate that Intermedilysin activity at sub-lethal concentrations causes the release of pro-inflammatory cytokine (IL-8) and can cause apoptosis in target cells. These data strongly indicate that Intermedilysin activity in-vivo is multifaceted and is not just a simple case of punching holes in target cells.

The application of novel mechanisms for disinfecting contaminated dental impression material. R.A. Whiley (with M. Patel).

An EPSRC funded 3 year study (Patel and Whiley) is being carried out on novel mechanisms for disinfecting dental impression materials. The study aims to develop an easy to use, economical material with self-disinfecting properties that uses a combination of strategies incorporated into a single formulation to maximize its effectiveness.

Innate Immune Mechanisms in the Oral Cavity – Dr R. P. Allaker

Role of Nitric Oxide:

The enterosalivary nitrate circulation appears to encourage nitrate reducing bacteria to reside within the oral cavity. Oral immunity may be enhanced via the action of microbial nitrate reductases and the subsequent production of nitric oxide (NO) from nitrite under acidic conditions. This theory has been examined in relation to oral disease (dental caries).  Further studies in collaboration with the William Harvey Institute are investigating the relationship between oral nitrate reducing microbial populations and blood pressure control as a result of vasodilatory NO production. The use of acidified nitrite as an antimicrobial is also being developed for a range of applications within the oral cavity

Role of Host Defence Peptides:

Host defence (antimicrobial) peptides, which are expressed at oral mucosal surfaces, are emerging as important effector molecules in linking the innate and adaptive immune responses. Previous work has demonstrated that adrenomedullin has antimicrobial activity against members of the oral microflora. Studies have also included investigations of adrenomedullin with respect to expression in oral epithelial cells and macrophages in response to oral bacteria.

The association between up regulation of AM and the NO cascade (NO synthase route), unites these areas of investigation. The regulation of these multi-functional molecules in response to periodontal bacteria is being examined. Their possible role as biomarkers of oral disease is under investigation. These studies also complement other projects on statherin and histatin salivary peptides.