Molecular Basis of Human Defensins as Novel Lipid II Binding Peptide Antibiotics

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DESCRIPTION (provided by applicant): The prevalence of resistant bacterial pathogens is rendering current antibiotics ineffective, and making it essential that new drugs be developed to fight infection. Defensins are antimicrobial peptides that protect man against bacterial and viral infections and have a wide range as potential anti-infective therapeutics. This proposal identifies Lipid II, an essential precursor in bacterial membrane biogenesis, as a potential target of defensin antibacterial activity for the first time. The overall objective of our study is to define functional and structural interactions between defensins and Lipid II. In the long term, we aim to apply the knowledge gained in our research towards the development of defensin-based antibiotic compounds targeting Lipid II to combat Gram-positive pathogenic infections.