Poly-l-Lysine Compacts DNA, Kills Bacteria, and Improves Protease Inhibition in Cystic Fibrosis Sputum

Rationale: Neutrophil serine proteases in cystic fibrosis (CF) lung secretions partially resist inhibition by natural and exogenous inhibitors, mostly because DNA impairs their control. Cationic polypeptides display the property of condensing DNA and retain antimicrobial properties. We hypothesized that DNA condensation by cationic polypeptides in CF sputum would result in a better control of CF inflammation and infection.Objectives: We examined whether poly-l-lysine would compact DNA in CF lung secretions and liquefy CF sputum, improve the control of extracellular proteases by exogenous inhibitors, and whether it displays antibacterial properties toward CF-associated bacteria.Methods: We used fluorogenic methods to measure proteolytic activities and inhibition by protease inhibitors in whole sputum homogenates from patients with CF before and after treatment with poly-l-lysine. Antibacterial properties of poly-l-lysine were measured in bacterial cultures and in whole CF sputum. Poly-l-lysine toxicity was...