The virulence of mixed infection with Streptococcus constellatus and Fusobacterium nucleatum in a murine orofacial infection model.

Orofacial infections are usually polymicrobial, and it is the microbial interactions of pathogenic species that cause tissue destruction. In this study, the microbial interaction between Streptococcus constellatus and Fusobacterium nucleatum was characterized using a murine orofacial infection model. A mixture of viable S. constellatus and F. nucleatum cells (both 2 x 10(8) CFU/mouse) was injected into the submandible; as a result, all of the test mice died. In contrast, none of the experimental animals monoinjected with either S. constellatus or F. nucleatum died (P<0.001), indicating that the synergism between the two resulted in the virulence. When a mixture of viable S. constellatus cells and a culture filtrate of F. nucleatum was tested, lethality and the bacterial cell count per lesion were significantly enhanced as compared with monoinjections (P<0.02). However, the virulence of F. nucleatum was not enhanced by infection of a culture filtrate of S. constellatus. The enhancement of virulence was observed even when viable S. constellatus cells and the culture filtrate of F. nucleatum were injected at separate sites. Heat treatment of the culture filtrate of F. nucleatum did not affect the enhancement. These results indicate that a heat-stable substance(s) produced by F. nucleatum contributes to the microbial synergy of S. constellatus and F. nucleatum in orofacial infections.