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

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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.