pH modulates the activity and synergism of the airway surface liquid antimicrobials β-defensin-3 and LL-37

Significance Although lungs are continuously bombarded by bacteria, pulmonary defense mechanisms normally keep them sterile. Those defenses include a complex mixture of antimicrobial peptides in the thin layer of liquid coating the airway surface. In cystic fibrosis, impaired bicarbonate secretion causes the airway surface liquid to become abnormally acidic. Here we found that an acidic pH impairs the ability of two key airway antimicrobial peptides, β-defensin-3 and LL-37, to kill bacteria. When these peptides were combined, they exhibited synergistic killing of Staphylococcus aureus , an organism that infects cystic fibrosis lungs. However, an acidic pH reduced their synergistic effect. Thus, an acidic pH impairs an important respiratory defense mechanism and may predispose the lungs of people with cystic fibrosis to bacterial infection.