The oral black-pigmented Bacteroides species have been clearly implicated as important microorganisms in the etiology of human periodontal disease, endodontic lesions, and certain severe oral and extra-oral soft tissue infections. Not only have certain of these species such as Bacteroides gingivalis and Bacteroides intermedius been strongly associated with oral infectious disease but recent studies find that certain strains within species are particularly virulent in the mouse and the guinea pig abscess models. This intra-species heterogeneity is also evident in our recent serological studies of B. gingivalis and B. intermedius. The present proposal seeks to define and characterize virulence factors associated with infections due to black-pigmented Bacteroides. The in vivo pathogenic potential of fresh clinical isolates and our own culture collection strains will be examined in the mouse and guinea pig abscess models and in gnotobiotic rats. We will then determine the phenotypic and genotypic traits of each strain by means of biochemical tests, gas-liquid chromatography, light and electron microscopy, serology, and DNA-DNA hybridization. These traits will then be correlated with in vivo pathogenicity of the black-pigmented Bacteroides to pinpoint virulence-associated factors. Since environment plays a key role in determining the expression of bacterial pathogenicity, we will determine the effect of growth rate, iron limitation, pH, and dissolved oxygen content on the expression of virulence- associated factors using the controlled growth environment of the chemostat. These studies will greatly expand the available information on the pathogenesis of human oral and extra-oral infections caused by the black-pigmented Bacteroides. This knowledge can then be used to formulate improved preventive and therapeutic measures for the control of these infections.