he proposed work is in response to NIH PA-04-093 involving NOVEL APPROACHES TO STUDY OLYMICROBIAL DISEASES. There is increasing evidence for the importance of polymicrobial infections in which microorganisms interact in a synergistic or inhibitory fashion, impacting on pathogenesis or the maintenance of health. The proposed studies involve very novel approaches for examining polymicrobial interactions known to occur in the development of pathogenic bacterial human dental plaque. Specifically, the studies will determine for the first time how factors involved in the virulence of and intercellular communication by specific oral bacteria are altered during the microbial interactions involved in dental plaque formation. Genomics and proteomics will be used to identify genes uniquely regulated during plaque formation. The utilization of continuous surfaces of primary plaque forming bacteria will allow detailed studies on the wide range of interbacterial interactions which occur during plaque development. Elucidation of the molecular details of plaque formation will enhance attempts to specifically reduce the pathogenic potential of biofilms known to be involved in the development of dental caries and the periodontal diseases. ? ? ?