STRUCTURAL ANALYSIS OF SIDEROPHORE BIOSYNTHESIS: AIDS ANTIBIOTICS

铁载体生物合成的结构分析：艾滋病抗生素

• 批准号: 7381956
• 负责人: AUDREY L LAMB
• 金额: $ 12.26万
• 依托单位: UNIVERSITY OF KANSAS LAWRENCE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7381956
• 关键词: STRUCTURAL; ANALYSIS; SIDEROPHORE; BIOSYNTHESIS; AIDS

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The long-term goal of our work is to understand in atomic detail the molecular mechanisms of siderophore production by Pseudomonas aeruginosa. The siderophores pyochelin and pyoverdin are virulence factors for this organism; if siderophore production is disrupted, the bacteria cannot acquire the iron required for survival in iron limiting environments such as the human host. Pseudomonas aeruginosa is notoriously antibiotic resistant and is able to colonize immuno-compromised patients and the lungs of patients with cystic fibrosis. Other deadly bacteria use siderophores in colonization of human tissues including plague bacteria (Yersinia pestis) and cholera bacteria (Vibrio cholerae). Therefore, structural information about the biosynthetic enzymes of pyochelin and pyoverdin may provide new anti-microbial targets not only for the rational drug design of antibiotics for CF therapy and secondary infections due to immunodepression in cancer, AIDS and burn patients, but also for the fight against bioterrorism. Our work in the subproject focuses on ornithine derivatization and incorporation into pyoverdin.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。我们工作的长期目标是详细了解铜绿假单胞菌产生铁载体的分子机制。铁载体脓螯素和脓毒素是该生物体的毒力因子；如果铁载体的产生被破坏，细菌就无法获得在铁限制环境（例如人类宿主）中生存所需的铁。众所周知，铜绿假单胞菌对抗生素具有耐药性，能够在免疫功能低下的患者和囊性纤维化患者的肺部定殖。其他致命细菌利用铁载体在人体组织中定殖，包括鼠疫细菌（鼠疫耶尔森菌）和霍乱细菌（霍乱弧菌）。因此，脓毒素和脓毒素生物合成酶的结构信息不仅可以为用于CF治疗和癌症、艾滋病和烧伤患者因免疫抑制引起的继发感染的抗生素的合理药物设计提供新的抗微生物靶点，而且可以为抗击癌症、艾滋病和烧伤患者的免疫抑制引起的继发感染提供新的抗微生物靶点。反对生物恐怖主义。我们在该子项目中的工作重点是鸟氨酸衍生化和并入pyoverdin。