Biofilm Formation in P. gingivalis: A Role for Capsule Expression

描述（由申请人提供）：细菌生物膜的发展是牙周病进展的基础。牙龈卟啉单胞菌是一种居住在口腔龈下缝隙的机会性病原体。这种革兰氏阴性厌氧菌是严重和慢性牙周病的病原体，这种疾病的特征是支持牙龈的组织被破坏，最终导致牙齿脱落。在我们的初步研究中，我们发现了一个以前未表征的染色体区域，参与了胶囊的合成。通过突变分析，我们确定胶囊表达会阻碍生物膜的发育，而缺乏胶囊表达则会促进生物膜的形成。我们的长期目标是在分子水平上充分表征这种预测的操纵子，并阐明胶囊合成和其他表面结构的协调表达如何与从生物膜内生命方式转变为浮游有毒状态相关。本应用程序的目的是确定控制该基因座表达的营养和环境参数，包括生物膜内表达研究。本应用中提出的研究具有重要意义，因为了解胶囊表达的控制是理解这种细菌从生物膜中持续存在的共生生物转变为毒性病原体的重要环节。作为这些研究的结果，我们将建立参与胶囊合成的基因表达谱，并确定胶囊表达与生物膜生长之间的关系。这一信息将有助于更好地理解指示牙龈卟啉卟啉菌成为致命病原体或继续保持低调并持续存在的信号。我们的结果将有可能导致新的治疗策略的发展，以调节这种口腔病原体的生物膜形成。

DESCRIPTION (provided by applicant): The development of a bacterial biofilm is fundamental to the progression of periodontal disease. Porphyromonas gingivalis is an opportunistic pathogen that resides within the subgingival crevice of the oral cavity. This Gram-negative anaerobe is a causative agent of severe and chronic cases of periodontal disease, a condition characterized by destruction of the tissue supporting the gums, and ultimately, tooth loss. In our preliminary studies, we identified a previously uncharacterized region of the chromosome involved in the synthesis of capsule. Through mutational analysis we determined that capsule expression blocks biofilm development, while a lack of capsule expression enhances biofilm formation. Our long-term goal is to fully characterize this predicted operon at the molecular level and to elucidate how capsule synthesis and the coordinate expression of other surface structures relates to the switch from an in-biofilm life-style to a planktonic virulent state. The objective of this application is to identify nutritional and environmental parameters that control the expression of this locus, including in-biofilm expression studies. The research proposed in this application is significant because understanding the control of capsule expression is a vital link to understanding the switch this bacterium makes from a commensal organism persisting in a biofilm to a virulent pathogen. As an outcome of these studies, we will have established the expression profile of genes involved in capsule synthesis and determined the relationship between capsule expression and biofilm growth. This information will lead to a better understanding of signals that either direct P. gingivalis to become a virulent pathogen or to continue to lie low and persist. Our results will potentially lead to the development of new therapeutic strategies for modulating biofilm formation by this oral pathogen.