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

基本信息

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
项目类别：
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

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

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项目摘要

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.

摘要项目2：特拉华大学 - 格莱姆 p01标题为高亲和力抗聚糖抗体的多维开发以抗击致命细菌感染旨在制定新的策略来打击细菌感染。整个项目赠款旨在开发理论抗体，以治疗抗细菌感染。项目2，标题为 “探测果仁糖修饰在金黄色葡萄球菌的抗体反应中的作用”将集中在细菌病原体金黄色葡萄球菌。金黄色葡萄球菌通常用青霉素或糖肽治疗；然而，已经出现了两种抗生素的先例抗性污渍。因此，世界健康组织已将其列入新抗生素的优先级清单。项目2将集中于细菌的合成来自金黄色葡萄球菌的肽聚糖（PGN）片段，非常重视所使用的两个修饰由SA修改PGN：乙酰化和壁teichoic酸（WTA）。作为细菌细胞壁和胡椒糖果对人类健康至关重要，它代表了一个极好的抗体靶标：人类没有这些细胞壁和它们对细菌至关重要。来自项目中合成的金黄色葡萄球菌的修改了肽聚糖片段将提供生产，表征和验证诊所所必需的生物学相关片段整个项目中的相关抗体。