P-113D, an antimicrobial peptide active against Pseudomonas aeruginosa, retains activity in the presence of sputum from cystic fibrosis patients

Antimicrobial peptides are a source of novel agents that could be useful fo r treatment of the chronic lung infections that afflict cystic fibrosis (CF ) patients. Efficacy depends on antimicrobial activity against the major pa thogens of CF patients, Pseudomonas aeruginosa, Staphylococcus aureus, and Haemophilus influenzae, in the environment of the CF patient's airway. We d escribe the in vitro efficacies of derivatives of histatins, which are hist idine-rich peptides produced by the salivary glands of humans and higher pr imates. 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-113D the mirror-image peptide with the ami no acid residues in the D configuration, was stable in sputum, was as activ e as P-113 against pathogens of CF patients in the absence of sputum and re tained significant activity in the presence of sputum from CF patients. Rec ombinant human DNase, which effectively liquefies sputum, enhanced the acti vity of P-113D in undiluted sputum against both exogenous (added) bacteria and endogenous bacteria. Because of its properties, P-113D shows potential as an inhalant in chronic suppressive therapy for CF patients.