Biofilms are central to oral ecology in health and disease. Historically, bacteria have been viewed as single-celled entities, but it is now clear that bacteria exist in stable communities that form specific and highly optimized architectures. The central hypothesis of this proposal is that the structures of these biofilms, as well as their persistence, requires a delicately orchestrated developmental program and communications network, characteristics traditionally reserved for the behavior of multicellular organisms. Just as tissue development requires the orchestrated and sequential nurturing of select cells and culling of others, the central hypothesis of this proposal predicts an analogous process that results in the outgrowth of bacterial cells in some areas of a colonized surface, and the culling of cells in others. The net affect of orchestrated cell growth and cell elimination is the production of a specifically designed biofilm architecture that optimizes nutrient access, waste elimination, protection from environmental hazards, and collectively, the ability to persist. An innovative aspect of this hypothesis is that the model predicts the existence of a "programmed cell death" pathway, as well as a specific, phase-varied antidote or neutralization pathway, both of which being critical for controlled development of the optimized biofilm architecture. The overarching goal of this research is to develop a rational basis for the design of new therapeutics to treat biota shift diseases of the oral cavity, such as gingivitis and periodontitis, while nurturing the formation or restoration of healthy oral flora. Streptococcus gordonii, an organism that is one of the first to colonize the tooth surface, and hence occurs at the base of the dental plaque consortium, will be the model organism of study.