Bacteriology Core

摘要 该协作P01应用程序的共同目标是靶向细菌病原体表面上的聚糖 使用抗体作为抗感染剂。我们假设，针对细菌聚糖的抗体具有高的 亲和性将有效地对抗耐药性细菌病原体。在具体项目中， 应用中，抗聚糖抗体将针对最严重的表面聚糖目标开发。 细菌病原体，包括耐甲氧西林金黄色葡萄球菌（Sa）、耐碳青霉烯类 肠杆菌科（肺炎克雷伯氏菌或Kp）和抗生素耐药淋病奈瑟氏菌（Ng），所有 这是世界卫生组织（WHO）的“高优先级”或“关键优先级”列表。这个目标 核心是满足P01团队的细菌学需求。我们最初的重点将是测试开发的反- 使用一系列测定法，包括抗体结合亲和力、抗体亲和力、抗体亲和力和抗体亲和力， 特异性和调理吞噬杀伤效力。接下来，我们将评估抗体对促进 补体介导的杀伤。同时，我们将测试针对活Kp和Ng的开发的抗聚糖抗体 病原体，并重复每个抗体结合和杀伤测定。最后，我们将测试选定的反萨 在小鼠皮肤感染模型中的抗体，并为P01团队提供了新的聚糖靶向线索， 发展这个合作项目的成果将包括更好地了解免疫系统如何 系统可以靶向抗药性细菌，以及如何利用免疫反应来控制细菌 生长而不产生阻力。

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.