Identification and Functional Characterization of Antimicrobial Peptides from the Bacterium Treponema pallidum

该研究计划的重点是加强对螺旋体细菌（梅毒和莱姆病等疾病的病原体）在人类宿主内的多微生物环境中生存和繁荣所使用的致病策略的理解。当前发现资助申请中包含的研究计划的方向集中在调查以下假设：高度成功的螺旋体细菌梅毒螺旋体（梅毒的病原体）的致病成功部分归功于其基因组编码的抗菌肽的补充。生物信息学分析表明，高达4%的T. pallidum基因组编码推定的抗微生物肽，一组小的带电荷的蛋白质，其功能是通过直接和间接的方式杀死竞争的细菌物种。当考虑在小T的上下文中时。苍白球基因组经历了广泛的基因组减少以仅保留最必需的基因，将如此大比例的基因组奉献给这类预测的功能性蛋白质表明这组蛋白质对病原体的成功至关重要。在这个提议中，预测的T. pallidum基因组的能力（目的1），这些抗菌肽杀死生物相关的竞争细菌物种在多微生物环境中遇到的T。将确定在感染期间梅毒螺旋体的抗微生物活性（目的2），并且这些抗微生物肽调节宿主免疫应答以增强竞争细菌的杀伤和梅毒螺旋体的存活的能力。将确定苍白球（目的3）。这些调查代表了一个新的研究线，以前没有在螺旋体领域进行。通过这些研究，我们将获得基本的知识，这将提高对T。pallidum建立成功的感染，并将在未来的研究中提供机会，以防止感染，针对这种致病性的战略。

This research program focuses upon enhancing understanding of the pathogenic strategies used by spirochete bacteria, causative agents of diseases such as syphilis and Lyme Disease, to survive and flourish in polymicrobial environments within a human host. The direction of the research program contained within the current Discovery Grant application is focused upon investigating the hypothesis that the highly successful spirochete bacterium Treponema pallidum, causative agent of syphilis, owes its pathogenic success in part to the complement of antimicrobial peptides encoded by its genome. Bioinformatic analyses show that up to 4% of the T. pallidum genome encodes for putative antimicrobial peptides, a group of small charged proteins that function to kill competing bacterial species via both direct and indirect means. When considered in the context of the small T. pallidum genome, which has undergone extensive genome reduction to retain only the most essential genes, dedication of such a large proportion of the genome to this predicted functional class of proteins suggest this group of proteins is critical to the success of the pathogen. In this proposal the full complement of predicted antimicrobial peptides encoded by the T. pallidum genome will be identified (Aim 1), the ability of these antimicrobial peptides to kill biologically relevant competing bacterial species in the polymicrobial environment encountered by T. pallidum during infection will be determined (Aim 2), and the ability of these antimicrobial peptides to modulate the host immune response to enhance killing of competing bacteria and survival of T. pallidum will be determined (Aim 3). These investigations represent a novel line of study that has not been previously performed in the spirochete field. Through these studies we will gain fundamental knowledge that will enhance understanding of the mechanism employed by T. pallidum to establish successful infection, and will provide opportunities in future studies to prevent infection by targeting this pathogenic strategy.