Bacteriology Core

细菌学核心

基本信息

批准号：
10549642
负责人：
ALEXANDER R HORSWILL
金额：
$ 24.41万
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/10549642
关键词：
Address Affinity Animal Model Antibiotic Resistance Antibiotic susceptibility Antibodies Antibody Specificity Bacterial Antibiotic Resistance Bacterial Infections Bacteriology Binding Biological Assay Clinical Community Healthcare Complement Complement 3b Deposition Development Dimensions Drug-resistant Neisseria Gonorrhoeae Exhibits Financial Hardship Goals Growth Human Immune Immune response Immune system Immunotherapy Infectious Agent Infectious Skin Diseases Invaded Klebsiella pneumoniae Knock-out Length of Stay Link Mediating Membrane Proteins Microbial Antibiotic Resistance Neisseria gonorrhoeae Outcome Peptide Hydrolases Peptidoglycan Phagocytosis Polysaccharides Protein Glycosylation Proteins Reporting Resistance Role Series Serum Skin Staphylococcus aureus Staphylococcus aureus infection Surface Teichoic Acids Testing Validation World Health Organization burden of illness carbapenem-resistant Enterobacteriaceae disorder control fighting health care settings methicillin resistant Staphylococcus aureus microbial disease microorganism mortality mouse model mutant neutrophil pathogen pathogenic bacteria resistance mechanism response

Address Affinity Animal Model Antibiotic Resistance Antibiotic susceptibility Antibodies Antibody Specificity Bacterial Antibiotic Resistance Bacterial Infections Bacteriology Binding Biological Assay Clinical Community Healthcare Complement Complement 3b Deposition Development Dimensions Drug-resistant Neisseria Gonorrhoeae Exhibits Financial Hardship Goals Growth Human Immune Immune response Immune system Immunotherapy Infectious Agent Infectious Skin Diseases Invaded Klebsiella pneumoniae Knock-out Length of Stay Link Mediating Membrane Proteins Microbial Antibiotic Resistance Neisseria gonorrhoeae Outcome Peptide Hydrolases Peptidoglycan Phagocytosis Polysaccharides Protein Glycosylation Proteins Reporting Resistance Role Series Serum Skin Staphylococcus aureus Staphylococcus aureus infection Surface Teichoic Acids Testing Validation World Health Organization burden of illness carbapenem-resistant Enterobacteriaceae disorder control fighting health care settings methicillin resistant Staphylococcus aureus microbial disease microorganism mortality mouse model mutant neutrophil pathogen pathogenic bacteria resistance mechanism response

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项目摘要

Abstract The collective goal of this collaborative P01 application is to target glycans on the surface of bacterial pathogens using antibodies as anti-infectious agents. We hypothesize that antibodies targeting bacterial glycans with high affinity will be effective in combating antibiotic-resistant bacterial pathogens. In the specific projects of this application, anti-glycan antibodies will be developed against selected surface glycan targets on the most serious bacterial pathogens, including methicillin-resistant Staphylococcus aureus (Sa), carbapenem-resistant Enterobacteriaceae (Klebsiella pneumoniae or Kp), and antibiotic resistant Neisseria gonorrhoeae (Ng), all of which are on the “High Priority” or “Critical Priority” list of the World Health Organization (WHO). The goal of this Core will be to serve the bacteriology needs of the P01 Team. Our initial focus will be to test the developed anti- glycan antibodies against live Sa pathogen using a series of assays, including antibody binding affinity, antibody specificity, and opsonophagocytic killing potency. Next, we will assess the impact of the antibodies on promoting complement mediated killing. In parallel we will test developed anti-glycan antibodies against live Kp and Ng pathogens and repeat each of the antibody binding and killing assays. Finally, we will test selected anti-Sa antibodies in a mouse model of skin infection and provide the P01 team with new glycan target leads for development. The outcomes of this collaborative project will include a better understanding of how the immune system can target antibiotic-resistant bacteria and how immune responses can be used to control bacterial growth without causing resistance to arise.

抽象的该协作P01应用的集体目标是靶向细菌病原体表面的聚糖使用抗体作为抗感染剂。我们假设靶向具有较高细菌糖的抗体亲和力将有效地对抗抗生素耐药细菌病原体。在特定项目中应用，将针对最严重的表面聚糖靶标开发抗甘油can抗体细菌病原体，包括耐甲氧西林金黄色葡萄球菌（SA），耐碳青霉烯肠杆菌科（克雷伯菌肺炎或KP）和抗生素耐药性淋病（NG）在世界卫生组织（WHO）的“高优先级”或“关键优先级”清单上。目标的目标核心将是满足P01团队的细菌学需求。我们最初的重点是测试已发达的抗使用一系列测定法，包括抗体结合亲和力，抗体，针对活体病原体的聚糖抗体特异性和调查性细胞杀死效力。接下来，我们将评估抗体对促进的影响补充介导的杀戮。同时，我们将测试针对Live KP和NG的已发达的抗聚糖抗体病原体并重复每种抗体结合和杀死测定法。最后，我们将测试选定的抗SA 皮肤感染的小鼠模型中的抗体，并为P01团队提供新的聚糖靶标线发展。该协作项目的结果将包括更好地了解免疫系统可以靶向抗生素耐药细菌，以及如何使用免疫回应来控制细菌生长而不会引起抵抗力。