Actinobacillus actinomycetemcomitans is an oral gram-negative microorganism which can cause severe extra-oral medical infections including bacterial endocarditis. Intra-orally, this organism has recently been implicated in the etiology of localized juvenile periodontitis and rapidly progressing adult periodontitis. We have reported three serotypes of oral A. actinomycetemcomitans based on heat stable cell surface antigens, a lipopolysaccharide-species common antigen, as well as heat-labile antigens common to serotypes a and b, and b and c. In localized juvenile periodontitis the prevalence of serotype b is increased while extra-oral A. actinomycetemcomitans infections are associated primarily with serotypes a and c. The importance of the serotype antigens is suggested by the finding that patients develop high levels of serum antibody to the A. actinomycetemcomitans serotype with which they are infected, and that antibody is required to opsonize A. actinomycetemcomitans prior to ingestion and killing by human polymorphonuclear leukocytes. The common antigens are important in the serodiagnosis of A. actinomycetemcomitans infections and may play a role in serotype shifts during localized juvenile periodontitis. This proposal will examine the pathogenesis of A. actinomycetemcomitans infections and specifically address the question of the association of A. actinomycetemcomitans serotypes with different clinical diseases. This will be accomplished by purification of the A. actinomycetemcomitans serotype antigens, the species common antigen and the serotype common antigens and by chemical, immunological, and structural characterization of the purified antigens. These antigens will be examined for their role in A. actinomycetemcomitans adherence to gram-positive plaque microorganisms and to human buccal epithelial cells. Patient serum antibody and local gingival crevicular fluid antibody response to these antigens will be qualitatively and quantitatively assessed at different times during localized juvenile periodontitis, rapidly progressing adult periodontitis, and extra-oral A. actinomycetemcomitans infection. We will also characterize antibody directed to these A. actinomycetemcomitans antigens for their respective abilities to function as heat-stable opsonins for phagocytosis and intracellular killing by human polymorphonuclear leukocytes. The proposed studies will provide insights into the influence of certain outer membrane antigens on the pathogenesis of A. actinomycetemcomitans infection and define this organism's principal serodiagnostic and """"""""protective"""""""" antigen(s) for development of clinical diagnostic tests and vaccines.
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