ROLE OF CU, ZN SOD IN A. ACTINOMYCETEMCOMITANS

描述（由申请人提供）：放线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因。这种细菌还能引起包括感染性心内膜炎在内的几种全身性疾病。放线菌作为毒力因子之一，能产生杀死人白细胞的白毒素，也能破坏红细胞。我们最近的研究强烈表明，白毒素与放线菌的Cu， Zn超氧化物歧化酶（Cu, Zn SOD）相互作用。细菌Cu， Zn sod具有保护病原体免受宿主炎症细胞氧化损伤的作用。铜、锌超氧化物歧化酶也被证明可以结合血红素，并可能在细菌获取铁和血红素中发挥作用。提出的研究旨在了解Cu， Zn SOD在放线菌comitans中的作用。1. 我将研究铜、锌SOD与放线菌白毒素的相互作用。2. 本文将对放线菌A.放线菌comitans中Cu、Zn SOD功能进行表征。这项研究将扩大我们对放线菌胞菌的生理和发病机制的认识，并可能使我们更好地了解一种重要口腔病原体的不同推定毒力因子之间的相互作用。

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.