Chlorate’s Potential as a Pro-Drug for Killing Antibiotic-Tolerant Pathogens in the Cystic Fibrosis Lung

Chronic lung infections are a major contributor to morbidity and mortality in cystic fibrosis (CF) patients. Perhaps the most notorious CF pathogen is Pseudomonas aeruginosa, which establishes decades-long lung infections despite aggressive antibiotic treatment. In part, drugs fail to clear P. aeruginosa lung infections because some pathogen populations exhibit antibiotic tolerance, a metabolic state that reduces a cell’s susceptibility to drugs. Antibiotic tolerance is associated with low metabolic activity, and P. aeruginosa growth is limited by oxygen availability in the largely hypoxic/anoxic CF sputum.