The Impact of Bacterial Fatty Acid Structure on the Activity of Antimicrobial Pep

细菌脂肪酸结构对抗菌肽活性的影响

• 批准号: 7880303
• 负责人: Antje Pokorny Almeida
• 金额: $ 21.6万
• 依托单位: UNIVERSITY OF NORTH CAROLINA WILMINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7880303
• 关键词: Acylation; Antibiotic Resistance; Antibiotics; Bacteria; Bacterial Model; Binding; Biological Models; Cell Culture Techniques; Cell membrane; Cells; Characteristics; Communities; Complex; Cyclopropanes; Environment; Fatty Acids; Goals; Health; Hospitals; Human; Immune system; Individual; Infection; Invaded; Lipids; Membrane; Membrane Lipids; Modeling; Organism; Peptides; Phase Transition; Phospholipids; Play; Predisposition; Relative (related person); Research; Role; Series; Specificity; Staphylococcus aureus; Structure; Study models; System; Testing; Therapeutic Index; Transition Temperature; Unsaturated Fats; Unsaturated Fatty Acids; Vesicle; antimicrobial; antimicrobial drug; antimicrobial peptide; bacterial resistance; combat; cyclopropane; design; in vivo; interest; lysin; membrane model; methicillin resistant Staphylococcus aureus; microorganism; novel strategies; pathogenic bacteria; preference; public health relevance; response

DESCRIPTION (provided by applicant): The goal of this project is twofold. First, we seek to study the impact of acyl chain structures typically found in bacterial lipids on antimicrobial peptide activity. Second, we will determine if acylation of an antimicrobial peptide with specific lipid structures will yield a more efficient antimicrobial agent while maintaining a high therapeutic index. To this date, most studies on the interaction of antimicrobial peptides with model bilayer systems have focused on readily available lipids that exist in only negligible quantities or not at all in cell membranes of many bacteria that represent a health threat to humans. We suggest that this approach has oversimplified the complex bacterial cell membrane and that the acyl chain structure of bacterial lipids plays a crucial role in the sensitivity of bacteria to antimicrobial peptides. We will test this hypothesis by studying peptide-membrane interactions in model systems using bacterial lipids of both natural and synthetic origin, and in bacterial cultures. We further suggest that the efficacy of antimicrobial peptides can be enhanced by the addition of a lipid anchor that, depending on its structure, facilitates peptide-induced membrane perturbation. Understanding the significance of lipids found in a variety of bacteria will help us to overcome bacterial adaptations to current antibiotics and to design new strategies of how to efficiently combat pathogenic bacteria. 1 PUBLIC HEALTH RELEVANCE: Bacterial resistance to conventional antibiotics is on the rise. Antimicrobial peptides are usually the first line of defense against invading microorganisms in most organisms, including humans. This project seeks to study the role of unique bacterial lipid structures in bacterial sensitivity to antimicrobial peptides and to develop new design strategies for novel antibiotics.

描述（由申请人提供）：该项目的目标是双重的。首先，我们试图研究通常在细菌脂质中发现的酰基链结构对抗菌肽活性的影响。第二，我们将确定具有特定脂质结构的抗微生物肽的酰化是否会产生更有效的抗微生物剂，同时保持高治疗指数。迄今为止，大多数关于抗菌肽与模型双层系统相互作用的研究都集中在现成的脂质上，这些脂质在许多对人类健康构成威胁的细菌的细胞膜中仅以可忽略不计的量存在或根本不存在。我们认为这种方法过度简化了复杂的细菌细胞膜，细菌脂质的酰基链结构在细菌对抗菌肽的敏感性中起着至关重要的作用。我们将测试这一假设，通过研究肽膜相互作用的模型系统中使用细菌脂质的天然和合成的来源，并在细菌培养。我们进一步表明，抗菌肽的功效可以通过添加脂质锚来增强，所述脂质锚根据其结构促进肽诱导的膜扰动。了解在各种细菌中发现的脂质的重要性将有助于我们克服细菌对当前抗生素的适应，并设计如何有效对抗病原菌的新策略。1 公共卫生相关性：细菌对常规抗生素的耐药性正在上升。抗菌肽通常是大多数生物体（包括人类）抵御入侵微生物的第一道防线。该项目旨在研究独特的细菌脂质结构在细菌对抗菌肽敏感性中的作用，并开发新的抗生素设计策略。