To colonize and persist in a host, bacterial pathogens must first adhere tightly to tissue surfaces and evade or overcome the host immune response as well as various non-immune anti-microbial activities. Our studies focus on the mechanisms used by pathogens to accomplish these tasks and we utilize the complex microbial community of the human oral cavity as a model to study these processes. We are investigating the mechanism of action of several protein toxins produced by oral pathogens. These proteins target human immune cells, e.g., macrophages, neutrophils and lymphocytes, and our goal is to understand the role that these toxins play in actively avoiding the immune response during infection. Organisms may also passively avoid the immune response by growing as a biofilm. We are interested in determining how oral pathogens identify a suitable niche and colonize the complex microbial community that exists in the oral cavity. The long term goal of these studies is to design novel therapeutics that target oral pathogens and prevent their colonization of the dental biofilm. The development and growth of complex microbial communities may also require communication among the cells within the biofilm and we are investigating mechanisms of bacterial cell-to-cell communication, focusing on quorum sensing systems that are present in oral pathogens. The goal of these studies is to determine if quorum sensing plays a role in allowing organisms to sense and respond to their local environment and the other bacteria that cohabit that environment.