ROLE OF CU, ZN SOD IN A. ACTINOMYCETEMCOMITANS

描述(申请人提供)：放线菌伴生放线杆菌是一种革兰氏阴性口腔病原体，是局部侵袭性牙周炎的病原体。这种细菌还可以引起几种全身性疾病，包括感染性心内膜炎。伴生放线菌作为一种致病因子，其产生的白毒素可杀死人的白细胞，也可破坏红细胞。我们最近的工作有力地表明，白毒素与伴生放线杆菌的铜，锌超氧化物歧化酶(铜，锌超氧化物歧化酶)相互作用。细菌铜锌超氧化物歧化酶具有保护病原体免受宿主炎症细胞氧化损伤的作用。铜、锌超氧化物歧化酶还被证明能与血红素结合，并可能在细菌获取铁和血红素的过程中发挥作用。这些研究试图了解铜、锌、超氧化物歧化酶在伴生放线菌中的作用。1.研究放线菌伴生菌产生的白毒素与铜、锌超氧化物歧化酶的相互作用。2.对伴生放线菌中铜锌超氧化物歧化酶的功能进行了研究。这项研究将扩大我们对伴生放线杆菌的生理学和致病机理的认识，并可能有助于更好地理解一种重要的口腔病原体的不同假定毒力因素之间的相互作用。

DESCRIPTION (provided by applicant): Actinobacillus actinomycetemcomitans is a Gram-negative oral pathogen that is the etiologic agent of localized aggressive periodontitis. This bacterium can also cause several systemic diseases including infective endocarditis. As one of virulence factors, A. actinomycetemcomitans produces leukotoxin that kills human leukocytes and can also destroy erythrocytes. Our recent work strongly suggests that leukotoxin interacts with Cu, Zn superoxide dismutase (Cu, Zn SOD) from A. actinomycetemcomitans. Bacterial Cu, Zn SODs have a role in protecting pathogens from the oxidative damage caused by host inflamatory cells. Cu, Zn SOD has also been shown to bind heme and potentially play a role in iron and heme acquisition by bacteria. The proposed studies seek to understand the role of Cu, Zn SOD in A. actinomycetemcomitans. 1. I will study the interaction between Cu, Zn SOD and leukotoxin from A. actinomycetemcomitans. 2. I will characterize Cu, Zn SOD function in A. actinomycetemcomitans. This study will expand our knowledge of the physiology and pathogenesis of A. actinomycetemcomitans and may lead to a better understanding of the interplay between different putative virulence factors of an important oral pathogen.