Characterization of A. actinomycetemcomitans leukotoxin mutants

描述（由申请人提供）：A。伴放线菌是一种革兰氏阴性细菌，是局部侵袭性牙周炎（侵袭性牙周炎）的病原体。A.伴放线菌也是与感染性心内膜炎有关的重要的HACECK细菌群的成员。它的毒力因子之一是一种有效的白细胞毒素，专门杀死白色血细胞，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的相似性，如E. coli中，但与A.伴放线菌我们拟研究白细胞毒素在A.放线菌共生菌的生理和致病机制，这可以导致更好地了解白细胞毒素作为毒力因子所发挥的作用，扩大我们的知识。更具体地说，我们提出的研究，旨在：1。参与白细胞毒素生物合成的新基因的鉴定。我们已经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，将确定和表征突变的性质。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修改的ItxC突变体中的白细胞毒素，并确定ItxC的白细胞毒素的活性的作用。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。我们正在研究这种细菌产生的毒素合成过程中的遗传学。我们的目标是了解这种毒素在疾病中所起的作用，以期提高我们预防或治疗由A.伴放线菌

DESCRIPTION (provided by applicant): 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.