Doctor of Philosophy (PhD)



Document Type



Antibiotic resistant bacteria pose one of the most urgent threats to public health. Pseudomonas aeruginosa is a multi-drug resistant bacterium for which new antibiotics are urgently needed. My research is focused on understanding and validating iron metabolism as a target for antibiotic development by analyzing the metabolic profiles of iron-starved P. aeruginosa cells caused by irreversibly trapping iron in bacterioferritin. Iron is an essential nutrient for bacteria; however, the reactivity of the Fe2+ ion and insolubility of the Fe3+ ion present significant challenges to bacterial cells. Iron storage proteins oxidize Fe2+ using O2 and H2O2 as electron acceptors to store Fe3+, thus relieving the bacteria of these challenges. The function of iron storage proteins was extensively investigated in Pseudomonas aeruginosa, a Gram-negative, multi-drug resistant opportunistic pathogen that affects immunocompromised individuals, burn victims, and cystic fibrosis patients. BfrB is the iron storage protein in P. aeruginosa, and the iron stored inside is mobilized, with the aid of bacterioferritin-associated ferrodoxin (Bfd), in late exponential and early stationary growth phases, when iron in the environment has been exhausted. Most importantly, inhibition of the BfrB-Bfd interaction in P. aeruginosa causes irreversible iron accumulation in BfrB and iron deficiency in the bacterial cytosol. Herein, we examine the global metabolic changes ensuing from iron starvation caused by the irreversible accumulation of iron in BfrB, which leads to iron limitation in the P. aeruginosa cytosol. Using proteomics and metabolomics-based approaches, it was found that inhibiting the BfrB-Bfd interaction causes differences in metabolites related to iron acquisition, amino acid, and energy metabolism. Likewise, the trapping of iron in bacterioferritin by a small molecule BfrB-Bfd inhibitor dysregulates metabolic homeostasis in the P. aeruginosa cell.



Committee Chair

Rivera, Mario

Available for download on Thursday, October 29, 2026