A major concern for global public health is the development of antimicrobial resistance (AMR) in bacterial pathogens limiting the use of current antibiotics. Bacterial pathogens are reported to contribute to approximately five-million associated deaths, with an estimated four-million deaths associated with ESKAPE pathogens including Pseudomonas aeruginosa. P. aeruginosa is a gram-negative opportunistic pathogen that poses a tremendous danger to immunocompromised patients. Additionally, P. aeruginosa is known to form biofilms that are hard to penetrate and can develop on medical implant devices, wounds, and in airways leading to chronic infection. Iron, an essential micronutrient for P. aeruginosa’s virulence and survival, is limited in the host during infection due to iron sequestration a process often termed nutritional immunity. P. aeruginosa can combat iron restriction by utilizing heme via its two non-redundant heme uptake systems, Pseudomonas heme uptake (Phu) and heme assimilation (Has) system. The Phu system, a high-capacity system, is the major route for heme acquisition while the Has system functions by sensing extracellular heme in the environment. The Has system comprises an extracellular hemophore, HasAp, that binds and releases heme to the outer-membrane receptor, HasR. The release of heme to HasR, triggers the extra cytoplasmic function (ECF) σ signaling cascade resulting in the transcriptional upregulation of HasAp while simultaneously translocating heme into the cell. Internalized heme is degraded by heme oxygenase (HemO) to release iron, carbon monoxide, and biliverdin isomers β and δ (BVIXβ/δ). Our lab has shown BVIXβ post-transcriptionally upregulates HasAp and further acts as a regulatory molecule in lifestyle adaptations associated with the transition to chronic infection. Currently, there are no effective therapies for P. aeruginosa infections accrediting to its classification as a “serious threat” by the CDC and a Priority 1 Pathogen for the development of new therapies by the WHO. We aim to develop therapies to attenuate P. aeruginosa infection by targeting the Has system with the use of Gallium-Salophen (GaSal) complexes that dampen the ECF σ signaling cascade leading to iron-dysregulation and reduced virulence. We hypothesize this mechanism of action has the potential to decrease the selective pressure for P. aeruginosa AMR.