P-113 d , an Antimicrobial Peptide Active against Pseudomonas aeruginosa , Retains Activity in the Presence of Sputum from Cystic Fibrosis Patients

Abstract

ABSTRACT Antimicrobial peptides are a source of novel agents that could be useful for treatment of the chronic lung infections that afflict cystic fibrosis (CF) patients. Efficacy depends on antimicrobial activity against the major pathogens of CF patients, Pseudomonas aeruginosa, Staphylococcus aureus , and Haemophilus influenzae , in the environment of the CF patient's airway. We describe the in vitro efficacies of derivatives of histatins, which are histidine-rich peptides produced by the salivary glands of humans and higher primates. P-113, a peptide containing 12 of the 24 amino acid residues of the parent molecule, histatin 5, retained full antibacterial activity and had a good spectrum of activity in vitro against the prominent pathogens of CF patients. However, P-113 was not active in the presence of purulent sputum from CF patients. In contrast, P-113 d , the mirror-image peptide with the amino acid residues in the d configuration, was stable in sputum, was as active as P-113 against pathogens of CF patients in the absence of sputum and retained significant activity in the presence of sputum from CF patients. Recombinant human DNase, which effectively liquefies sputum, enhanced the activity of P-113 d in undiluted sputum against both exogenous (added) bacteria and endogenous bacteria. Because of its properties, P-113 d shows potential as an inhalant in chronic suppressive therapy for CF patients.