Iron Homeostasis in the CF Lung

Pseudomonas aeruginosa is responsible for life-long and debilitating chronic lung infections in cystic fibrosis (CF) patients. Within the CF lung, P. aeruginosa evolves considerably and becomes increasingly resistant to antibiotic therapy. P. aeruginosa requires iron for infection, a requirement that may be exploited for the development of new and effective antibiotic treatments. P. aeruginosa uses a variety of strategies to acquire iron, one of which relies on a small iron-scavenging molecule called pyoverdine. Pyoverdine is required for acute infections, but the ability of some P. aeruginosa strains to make pyoverdine is lost after several years of chronic CF lung infection. In collaboration with the Wilks laboratory, we previously showed that heme acquisition is enhanced in CF isolates over time, indicating heme is an abundant source of iron in the CF lung. We are currently working to understand the molecular basis of these adaptations.

Infection of the CF lung is not limited to just P. aeruginosa, and several reports have demonstrated that interactions between distinct microbial pathogens affects the outcome of disease. In particular, the Gram-positive CF lung pathogen Staphylococcus aureus, which is commonly found in younger CF patients, can serve as an iron source for P. aeruginosa. In an effort to define the molecular basis of this phenomenon, we are using mass spectrometry to determine the impact of iron on the production of metabolites with both signaling and antimicrobial capabilities, combined with transcriptome analysis of iron regulatory pathways. These studies are expected to identify novel metabolites that drive polymicrobial interactions, as well as the biosynthetic and regulatory pathways that mediate their production.

See more: Iron and antibiotic resistance in P. aerugionsa