COBRE: UOK HSC: P3: BIOFILM FORMATION BY ACTINOBACILLUS ACTINOMYCETEMCOMITANS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。伴放线放线杆菌(Aa)是一种革兰氏阴性嗜酸细菌，与早期牙周疾病、皮下脓肿和心内膜炎有关。除了这种细菌产生各种潜在的毒力因子外，人们对再生障碍性贫血的发病机制知之甚少，其中包括一种有助于疾病的强有力的白毒素(36)。许多AA临床分离株最显著的特征之一是能够形成致密紧密堆积的生物膜，这些生物膜很难分离(11-13，30)。这种紧密的黏附与AA在大鼠口腔中定植的能力有关，可能对人类的持久性很重要(55)。在目前的应用中，我们提出了旨在了解AA生物膜形成所需过程的实验。我们将使用最近完成的AA基因组来设计基因组规模的策略，以研究AA生物膜的发育。虽然已经发表了一些关于AA生物膜形成的研究，但对生物膜形成的发育途径几乎一无所知。我们的目标是确定对再生障碍性关节炎的附着和生物膜形成至关重要的过程，并评估它们对发病机制和口腔内持久性的影响。

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.