Invasion and Adhesion of Periopathogens

描述(申请人提供)：放线菌伴生放线杆菌(AA)是一种非运动性、革兰氏阴性兼性球菌，定植于人类口腔和上呼吸道。压倒性的微生物、免疫学和临床证据表明，AA与局限性青少年牙周炎和快速难治性牙周病的发病机制有关。这种病原体与其他严重的人类感染有关，如心内膜炎、软组织脓肿，以及最近的心血管疾病。牙周组织被认为是这些口外感染的宿主，尽管人们对这种病原体在组织中渗透和传播的机制知之甚少。这种牙周病原体已在体外侵袭上皮细胞，并定位于上皮细胞内，并在感染者的组织活检中发现于亚上皮细胞层。我们的实验室已经证明，再生障碍性贫血利用微管进行细胞内转运和退出上皮细胞。这些数据表明，微管在再生障碍性贫血的传播和移动中起着关键作用，并首次提供了宿主细胞内病原体的扩散可能涉及微管篡夺的证据。为了进一步了解这种独特的相互作用，我们建议1)鉴定和表征参与与微管相互作用的细菌大分子(S)，以及2)表征与AA相互作用的上皮细胞微管的成分(S)。对这些成分的鉴定对于了解这种病原体在口腔中生存并扩散到更深层次组织的过程将是重要的。

DESCRIPTION (provided by applicant): Actinobacillus actinomycetemcomitans (Aa) is a non-motile, Gram-negative facultative coccobacillus, which colonizes the human oral cavity and upper respiratory tract. Overwhelming microbial, immunological and clinical evidence implicates Aa in the pathogenesis of localized juvenile periodontitis and cases of rapid and refractory periodontal disease. This pathogen has been associated with other serious human infections such as endocarditis, soft tissue abscesses, and more recently cardiovascular disease. The periodontium has been implicated as the reservoir of these extraoral infections, although little is known about the mechanisms this pathogen utilizes to infiltrate and disseminate in tissues. The invasion into epithelial cells in vitro is well established and this periodontopathogen has been localized inside epithelial cells and found in sub epithelial cell layers in tissue biopsy from infected individuals. Our laboratory has demonstrated that Aa utilizes microtubules for intracellular trafficking and exit from epithelial cells. The data suggest that microtubules play a critical role in the spread and movement of Aa and provide the first evidence that host cell dispersion of an intracellular pathogen may involve the usurpation of microtubules. To further understand this unique interaction, we propose to 1) identify and characterize the bacterial macromolecule(s) that are involved in the interaction with microtubules and 2) characterize the component(s) of the epithelial cell microtubule asters that interact with Aa. The identification of these components will be important in understanding the processes that this pathogen uses to survive in the oral cavity and disperse into deeper tissues.