Iron and Antibiotic Resistance

Pseudomonas aeruginosa infections are often recalcitrant to antimicrobial therapy due to the formation of biofilms, which are 10- to 100-fold more resistant to available antimicrobial therapies than non-biofilm growing cells. Over the past thirty years, several key mediators of P. aeruginosa biofilm formation have been identified. Notably, iron has been shown by numerous studies to be critical for the establishment and maintenance of biofilms by P. aeruginosa. However, the mechanism(s) by which iron contributes to biofilm formation remain(s) unknown.

Iron and tobramycinOur lab previously showed that iron-replete conditions enhance resistance of P. aeruginosa non-biofilm growth against tobramycin and tigecycline. This is demonstrated in the figure to the right, in which we used ETEST®s to determine the effects of iron supplementation on tobramycin resistance (figure adapted from Oglesby-Sherrouse, et al, 2014). Additionally, we showed that iron increases the minimal concentration of tobramycin required to eradicate biofilms, and that iron depletion blocks the previous observed induction of biofilm formation by sub-inhibitory concentrations of tobramycin. These studies suggest iron and tobramycin signal through overlapping regulatory pathways to affect biofilm formation.

Currently, we are working to understand how iron and other metals affect antibiotic resistance and biofilm formation by P. aeruginosa. With this information, we hope to target the acquisition of iron and other metals to increase sensitivity of P. aeruginosa to therapeutic agents.