The Effect of Streptococcus anginosus on Human Oral Keratinocyte Proliferation

Background: Streptococcus anginosus, part of the Streptococcus milleri-group, is an opportunistically pathogenic bacterium associated with purulent dental, liver and brain abscesses. Furthermore, there is increasing evidence to associate S. anginosus infection with the incidence of oral cancer and upper respiratory tract carcinoma. The mechanisms by which infection might be associated with increased risks of carcinogenesis are unclear; in fact, little is known of the interactions that occur between this bacterial species and its host's epithelial cells. However, previous studies show that S. anginosus is capable of producing virulence factors that increase the rate of proliferation of eukaryotic cells, such as endothelial fibroblasts. Whether a similar effect is seen with human keratinocytes has not previously been reported. The enhanced proliferation of epithelial keratinocytes has been shown to promote the initiation of carcinogenesis.

Objective: To determine whether S. anginosus affects the proliferation rate of human oral keratinocytes in vitro.

Methods: An immortalized oral mucosal keratinocyte cell line (OKF6-h-Tert-1) was used to model human oral epithelial cells. Bacterial supernatants from cultures of several strains of S. anginosus, including the type strain and isolates obtained from within oral carcinoma tissue samples, were obtained and the protein content quantitated. Keratinocytes were then cultured in the presence of a range of concentrations of bacterial supernatant protein (10ng/ml – 100mg/ml) from each strain. Rates of cell proliferation were measured by MTT assay.

Results: Contrary to what was observed with endothelial fibroblasts, the presence of supernatant from S. anginosus decreased the rate of keratinocyte proliferation in a dose-dependant manner. There were no significant differences apparent between the bacterial strains.

Conclusions: Protein produced by S. anginosus appears to suppress the proliferation of human oral keratinocytes. Further work is required to ascertain the precise nature of this interaction and what other effects, if any, this bacterium has on these human cells.