The applicant notes that necrotizing ulcerative periodontitis (NUP) in seropositive patients is a rapidly destructive oral infection with a rapid onset of inflammation, deep bone pain and associated destruction of oral hard and soft tissues. The applicant notes that histologic and microbiologic examinations of the tissues involved in NUP reveal it to be an acute necrotizing ulcerative gingivitis (ANUG) superimposed on a rapidly progressing periodontitis. Spirochetes of various sizes are significant members of the microbiota in the gingival sulcus and may increase dramatically during the progressive periodontitis and are implicated as etiologic agents in ANUG. The applicant notes that the anaerobic nature of the spirochetes places them in genus treponemes and that they are only four oral treponemes species cultivated: T. denticola, T. vincent ii, T. socranskii, and T pectinovorom. This proposal is a collaborative effort involving clinical periodontics, molecular genetics and microbiology and immunology and to test the hypothesis that oral treponemes from ANUG-like and NUP-like lesions from HIV seropositive subjects possess greater destructive capacity (virulence) than isolate from HIV seropositive patients with linear gingival erythema(LGE), HIV seronegative adult periodontitis, rapidly progressive periodontitis, and chronic gingivitis subjects. In addition, they hypothesize that in the selective environment of the immunocompromised host there is an emergence of treponema spp. which are not routinely found in HIV seronegative subjects. The destructive ability of the species treponemes as well as any newly identified species will be examined in an in vivo murine abscess model and in a calvarial destruction model. There are three specific aims identified with the application and they are as follows: (1) to isolate and biochemically and morphologically characterize members of the genus Treponema from LGE, ANUG-like and NUP-like periodontal lesions in HIV seropositive subjects and compare them to medically healthy HIV seronegative subjects with chronic gingivitis, ANUG, adult periodontitis, and rapidly progressive periodontitis; (2) to determine the soft tissue characteristics of these treponema strains as identified in Specific Aim 1 in an in vivo murine abscess model; and (3) to determine the bone destructive characteristics of these treponema strains in an in vivo murine calvarial model developed in the laboratory of the applicant. In relation to the various specific aims, the applicant has posed questions to be answered by the research.
Specific Aim 1 - What is the distribution of the genus and species of spirochetes in subgingival plaque using nucleic acid probe technology; 2 - Are the growth characteristics and morphological characteristics different in the treponema strains that can be isolated and cultivated from patients with more aggressive disease; 3 - Does the production of trypsin-like enzymes, other proteases and expression of specific fibroblasts binding proteins and hemolysin production differ in the treponemes that can be isolated and cultivated from patients with more aggressive disease. In relation to Specific Aim 2, they posed the questions (1).Do treponemes that can be isolated and cultivated from more aggressive disease exhibit increased soft tissue destruction in a murine model and (2). Do sera derived from various patient groups have a capacity to modify soft tissue destruction caused by treponemes from aggressive disease. In relation to Specific Aim 3, the applicant questions: (1). Do treponemes that can be isolated and cultivated from more aggressive disease exhibit bone destruction; and (2). Do sera derived from various patient groups have the capacity to modify bone destruction that may be elicited by treponemes derived from aggressive disease.
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