Probing the role of peptidoglycan modification in the antibody response to Staphylococcus aureus

探讨肽聚糖修饰在金黄色葡萄球菌抗体反应中的作用

• 批准号: 10549646
• 负责人: Catherine Leimkuhler Grimes
• 金额: $ 21.46万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-09 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10549646
• 关键词: Acetylation; Acetylmuramyl-Alanyl-Isoglutamine; Affinity; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Antibodies; Antibody Response; Antibody Therapy; Antigens; Bacteria; Bacterial Infections; Carbohydrates; Cell Wall; Complex; Coupled; Coupling; Crosslinker; Data; Delaware; Development; Dimensions; Disaccharides; Elements; Family; Generations; Glycopeptides; Gram-Negative Bacteria; Grant; Health; Human; Human body; Infection; Innate Immune Response; Libraries; Link; Methicillin; Methicillin Resistance; Microbial Biofilms; Modification; Molecular Target; Monosaccharides; Morbidity - disease rate; Penicillins; Peptides; Peptidoglycan; Polymers; Polysaccharides; Positioning Attribute; Production; Reproducibility; Resistance; Role; Staphylococcus aureus; Structure; Teichoic Acids; Testing; Therapeutic; Therapeutic antibodies; Universities; Vancomycin; Vancomycin Resistance; Vertebral column; Viral; Virulence; Virulent; Work; World Health Organization; bacterial resistance; clinically relevant; combat; fighting; flexibility; glycosylation; methicillin resistant Staphylococcus aureus; monomer; mortality; novel; novel strategies; particle; pathogen; pathogenic bacteria; phosphodiester; programs; resistant strain; success

ABSTRACT Project 2: University of Delaware - Grimes The P01 entitled Multidimensional development of high-affinity anti-glycan antibodies to fight deadly bacterial infections aims to develop novel strategies to combat bacterial infections. The whole project grant aims to develop therapeutic antibodies for the treatment of bacterial resistant infections. Project 2, entitled “Probing the role of peptidoglycan modification in the antibody response to Staphylococcus aureus” will focus on bacterial pathogen Staphylococcus aureus. S. aureus is typically treated with penicillin or glycopeptides; however precedent resistant stains to both classes of antibiotics have emerged. As such, the World Health Organization has placed it on the priority list for new antibiotics. Project 2 will focus on the synthesis of bacterial peptidoglycan (PGN) fragments from Staphylococcus aureus, with a strong emphasis on two modifications used by Sa to modify PGN: acetylation and wall teichoic acids (WTA). As the bacterial cell wall and peptidoglycans are critical to human health it represents an excellent antibody target: humans do not have these cell walls and they are essential to bacteria. The modified peptidoglycan fragments from S. aureus synthesized in the project will provide the biologically relevant fragments necessary to produce, characterize and validate the clinically relevant antibodies throughout this entire project.

项目2：特拉华州格里姆斯大学 P01题为高亲和力抗聚糖抗体的多维开发，以对抗致命的 bacterial infections旨在开发对抗细菌感染的新策略。整个项目补助金 旨在开发用于治疗细菌耐药性感染的治疗性抗体。项目2，题为 “探索肽聚糖修饰在金黄色葡萄球菌抗体应答中的作用”将集中在 细菌病原体金黄色葡萄球菌S.金黄色葡萄球菌通常用青霉素或糖肽治疗; 然而，已经出现了对这两类抗生素都具有抗性的菌株的先例。因此，世界卫生 该组织已将其列入新抗生素的优先名单。项目2将集中在细菌的合成 来自金黄色葡萄球菌的肽聚糖（PGN）片段，着重强调使用的两种修饰 通过Sa对PGN进行修饰：乙酰化和壁磷壁酸（WTA）。因为细菌的细胞壁和肽聚糖 对人类健康至关重要，它代表了一个极好的抗体靶点：人类没有这些细胞壁， 它们是细菌所必需的。对S.项目合成的金黄色葡萄球菌 将提供生产、表征和验证临床所需的生物学相关片段 相关的抗体。