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

人类防御素作为新型脂质 II 结合肽抗生素的分子基础

• 批准号: 8191604
• 负责人: Erik de Leeuw
• 金额: $ 23.03万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8191604
• 关键词: Acute; Anabolism; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotic Resistance; Antibiotics; Bacteria; Bacterial Infections; Binding; Biochemical; Biological Assay; Cell Wall; Charge; Clinical; Defensins; Development; Disulfides; Electrostatics; Family; Frequencies; Goals; Gram-Positive Bacteria; Host Defense; Human; Infection; Knowledge; Lead; Light; Lipid Binding; Lipids; Membrane; Molecular; Multi-Drug Resistance; Mutate; Mutation; Natural Immunity; Outcome; Patients; Peptide Antibiotics; Peptides; Pharmaceutical Preparations; Prevalence; Prevention; Reporting; Research; Resistance; Therapeutic; Time; Validation; Virus Diseases; analog; antimicrobial; antimicrobial drug; antimicrobial peptide; bacterial resistance; base; combat; disulfide bond; fighting; human neutrophil peptide 1; infectious disease treatment; innovation; insight; killings; man; membrane biogenesis; microbial; novel; pathogen; research study

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. PUBLIC HEALTH RELEVANCE: The escalating frequency of antibiotic resistant infections combined underscores the critical need to develop novel antibiotics. This project describes for the first time the interaction between defensins, naturally occurring antimicrobial compounds in humans and Lipid II, essential in the formation of bacterial membranes. Our research sheds new light on how defensins kill bacteria and is an important first step towards the development of these natural peptides as novel, effective antibiotic agents to combat infections.

描述（由申请人提供）：耐药细菌病原体的流行使目前的抗生素无效，因此必须开发新药来对抗感染。防御素是保护人体免受细菌和病毒感染的抗菌肽，具有广泛的抗感染治疗潜力。本文首次确定了在细菌膜生物发生过程中必不可少的前体脂质II作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脂质II之间的功能和结构相互作用。从长远来看，我们的目标是将我们在研究中获得的知识应用于开发基于防御素的靶向脂质II的抗生素化合物，以对抗革兰氏阳性致病性感染。