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.
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