This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Actinobacillus actinomycetemcomitans (Aa) is a gram-negative capnophilic bacterium implicated in early onset periodontal diseases, subcutaneous abscesses, and endocarditis. Little is known about the mechanisms of pathogenesis in Aa, other than this bacterium produces a variety of potential virulence factors including a potent leukotoxin which contributes to disease (36). One of the most striking features of many clinical isolates of Aa is the ability to form dense tightly-packed biofilms which are difficult to dissociate (11-13, 30). This tight adherence has been linked to the ability of Aa to colonize the mouths of rats and may be important for persistence in humans (55). In the current application, we propose experiments designed to understand the processes required for Aa biofilm formation. We will use the recently completed Aa genome to design genome-scale strategies for studying Aa biofilm development. Although several studies involving Aa biofilm formation have been published, virtually nothing is known about the developmental pathway for biofilm formation. Our goals are to identify processes important for attachment and biofilm formation in Aa and evaluate their impact on pathogenesis and persistence in the oral cavity.
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