Bacteriology Core

细菌学核心

• 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
• 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

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.

摘要 这个协作P01应用程序的共同目标是针对细菌病原体表面的葡聚糖 使用抗体作为抗感染剂。我们假设针对细菌多糖的抗体具有很高的 亲和力将有效地对抗抗药性细菌病原体。在这个项目的具体项目中 应用方面，将研制出针对选定的糖链表面最严重的靶点的抗糖蛋白抗体 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(肺炎克雷伯氏菌或Kp)和耐药淋球菌(Ng)，均为 它们被列入世界卫生组织(世卫组织)的“高度优先”或“严重优先”名单。这样做的目的是 核心将是服务于P01团队的细菌学需求。我们最初的重点将是测试开发的反 利用一系列检测方法，包括抗体结合亲和力、抗体 特异性和吞噬细胞杀伤力。接下来，我们将评估抗体对促进 补体介导的杀伤。同时，我们将测试开发的针对活体KP和Ng的抗多糖抗体。 并重复每一种抗体结合和杀灭试验。最后，我们将测试选定的反SA 小鼠皮肤感染模型中的抗体，并为P01团队提供了新的糖链靶向线索 发展。这一合作项目的成果将包括更好地理解免疫系统如何 系统可以针对抗药性细菌，以及如何利用免疫反应来控制细菌 在不引起抗性的情况下生长。