Funded Projects

This project bridges basic science, engineering, and clinical application across complementary research groups at UB. Dr. Blaine Pfeifer uses a bio-engineering approach termed heterologous biosynthesis to produce a class of compounds called siderophores, known for their ability to sequester metal species. Dr. Andy Gulick also studies siderophores, in particular, their base biosynthetic and structural details. Drs. Pfeifer and Gulick will focus on producing siderophores, yersiniabactin and aerobactin, specific to their research groups, respectively. These compounds will then be chelated with a range of metal species (including copper and gallium) for targeted delivery to both Gram-positive and -negative pathogenic microbes. Dr. Thomas Russo focuses on clinical infectious disease and will oversee the antibiotic testing aspects of this project. With this group and range of roles introduced, the larger hypothesis behind this project is that certain metals (with gallium serving as a good example) have demonstrated toxicity towards unwanted pathogenic bacteria. However, bulk administration of metals to a patient at the levels potentially required for anti-microbial effectiveness pose issues in both safety and economics. We believe that the effectiveness of metal-based anti-microbial therapy can be improved and made more effective with the targeted delivery of such metals once chelated to siderophore products. Thus, the siderophore serves as a delivery vehicle, and our group is uniquely poised to first access these siderophore compounds and then assess their anti-microbial effectiveness once chelated to select metals. As such, we present a team capable of producing siderophores with the goal of testing their metal-chelated forms for novel antibiotic activity. Success will support continued collaboration and serve as key preliminary data towards similar anti-microbial themes to be packaged as a subsequent NIH R01 application.