Degree
Doctor of Philosophy (PhD)
Department
Chemistry
Document Type
Dissertation
Abstract
The world health organization (WHO) published a priority list of antimicrobial resistant organisms that are in critical need for novel targets and therapeutics. Among the critical category includes Gram-negative P. aeruginosa and A. baumannii. Iron is essential for all domains of life and presents a vulnerable target to exploit for antimicrobial resistant pathogens. Our research group focuses on iron storage proteins and disrupting iron homeostasis by targeting a specific protein-protein interaction. Our group has identified that the binding site of bacterioferritin (Bfr) and its cognate partner bacterioferritin-associate ferredoxin (Bfd) interaction is crucial for iron mobilization from within Bfr and into the cytosol. These findings prompted for the discovery a fragment library and a structure guided approach to develop 4-aminoisoindoline-1,3-dione derivatives that inhibit the binding site of Bfr:Bfd and irreversibly trapping iron within the Bfr core, disrupting iron homeostasis.
This dissertation will explore derivatizing the 4-aminoisoindoline-1,3-dione derivatives, and conducting a full structure-activity relationship study for both P. aeruginosa and A. baumannii to gain insight and understanding of how these molecules are effective against these pathogens. This dissertation will also investigate possible reasons for as to why these compounds are bacteriostatic against planktonic P. aeruginosa and studying the three phases of growth (lag, exponential, and stationary phase). A proteomic analysis was also conducted to determine the global impact of these small molecules against P. aeruginosa. Lastly, this dissertation will briefly show that these small molecules are effective against other Gram-negative pathogens that also have conserved sequences for Bfr and Bfd.
Date
7-16-2026
Recommended Citation
Behm, Alexanndra M., "INVESTIGATING THE STRUCTURE-ACTIVITY RELATIONSHIP OF SMALL MOLECULES DESIGNED TO DISRUPT IRON HOMEOSTASIS BY INHIBITING THE BACTERIOFERRITIN-FERREDOXIN COMPLEX IN PSEUDOMONAS AERUGINOSA" (2026). LSU Doctoral Dissertations. 7154.
https://repository.lsu.edu/gradschool_dissertations/7154
Committee Chair
Mario Rivera
LSU Acknowledgement
1
LSU Accessibility Acknowledgment
1