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

描述(申请人提供)：耐药细菌病原体的流行使目前的抗生素无效，这使得开发新的药物来对抗感染是必要的。防御素是一种抗菌肽，可保护人类免受细菌和病毒感染，作为潜在的抗感染治疗药物具有广泛的应用前景。这项提议首次将细菌膜生物发生中的重要前体Lipid II确定为防御素抗菌活性的潜在靶点。我们研究的总体目标是确定防御素和Lipid II之间的功能和结构相互作用。从长远来看，我们的目标是将研究中获得的知识应用于针对Lipid II的基于防御素的抗生素化合物的开发，以对抗革兰氏阳性病原体感染。

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.