Characterization of A. actinomycetemcomitans leukotoxin mutants

A.伴放线菌是一种革兰氏阴性菌，是局部侵袭性的病原体， 牙周炎（periodontitis，PPH）。A.伴放线菌也是重要的HACECK组的成员， 感染性心内膜炎的细菌它的毒力因子之一，一种强效白细胞毒素， 特别是白色血细胞，也可以破坏红细胞。白细胞毒素是RTX毒素的一员。 目前对白细胞毒素在A. actinomycetemcomitans是基于 与其他细菌系统如E.但这些系统之间存在一些差异 和A.伴放线菌我们拟研究白细胞毒素在A. 放线菌共生扩大我们的知识，生理和发病机制，这种生物体 这可以导致更好地理解白细胞毒素作为毒力因子所起的作用。更 具体而言，我们建议开展以下研究： 1.参与白细胞毒素生物合成的新基因的鉴定。我们分离出了白细胞毒素突变体， 有几个突变映射在白细胞毒素操纵子之外的某个地方我们提出的实验 识别和表征突变的性质。 2.确定ItxC在白细胞毒素修饰和活性中的作用。我们提出的实验， 这将使我们能够研究ItxC突变体中白细胞毒素的修饰，并确定ItxC在细胞凋亡中的作用。 白细胞毒素活性。 本研究将扩大我们对A.伴放线菌 A.伴放线菌是一种口腔病原体，可引起牙周病和心脏病。我们正在研究 与这种细菌产生的毒素的合成有关的遗传学。我们的目标是了解 这种毒素在疾病中的作用，希望能提高我们预防或治疗疾病的能力， 由A.伴放线菌

A. actinomycetemcomitans, a gram-negative bacterium, is the causative agent of localized aggressive periodontitis (LAP). A. actinomycetemcomitans is also a member of the important HACECK group of bacteria implicated in enfective endocarditis. One of its virulence factors, a potent leukotoxin, kills specifically white blood cells and can also destroy erythrocytes. Leukotoxin is a member of the RTX toxins. Much of the present knowledge in the biosynthesis of leukotoxin in A. actinomycetemcomitans is based on similarity with other bacterial systems, such as E. coli, but some differences exist between those systems and A. actinomycetemcomitans. We propose to study the biosynthesis of leukotoxin in A. actinomycetemcomitans to expand our knowledge of the physiology and pathogenesis of this organism which can lead to a better understanding of the role played by leukotoxin as virulence factor. More specifically, we propose studies that aim to: 1. Characterize of novel genes involved in leukotoxin biosynthersis. We have isolated leukotoxin mutants, and several mutations map somewhere outside of the leukotoxin operon. We propose experiments that will identify and characterize the nature of the mutations. 2. Determine the function of ItxC in the modification and activiy of leukotoxin. We propose experiments that will allow us to study modification of leukotoxin in ItxC mutants and to determine the role of ItxC on the activity of leukotoxin. This study will expand our knowledge of the genetics of leukotoxin production in A. actinomycetemcomitans. A. actinomycetemcomitans, an oral pathogen, causes periodontal and heart disease. We are studying the genetics involved in the synthesis of a toxin produced by this bacterium. It is our goal to understand the role played by this toxin in the disease with the hopes of enhancing our ability to prevent or treat diseases caused by A. actinomycetemcomitans.