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

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-113D, the mirrorimage 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-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.

Human Salivary Mucin MUC7 12-Mer-land 12-Mer-dPeptides: Antifungal Activity in Saliva, Enhancement of Activity with Protease Inhibitor Cocktail or EDTA, and Cytotoxicity to Human Cells

“…Similarly, the all-D-amino-acid isomer of Hsn5 12-mer (P113-D) was as active against C. albicans as the natural L form. In addition, P113-D but not the L peptide was active against respiratory bacteria in the presence of sputum from cystic fibrosis patients (23).…”

Different Anti- Candida Activities of Two Human Lactoferrin-Derived Peptides, Lfpep and Kaliocin-1

“…when standard MIC determinations were performed in RPMI 1640 or PG broth (containing 1% peptone) (data not shown). A similar inhibitory effect, caused by medium components, was previously observed when other anticandidal peptides were tested and was solved by using nonstandardized synthetic media (26,27). However, these alternative media were not suitable for testing the susceptibility of the Candida strains to kaliocin-1 due to the presence of an inhibitory salt concentration.…”

“…Similar salt-sensitive antimicrobial activity has been reported for many antimicrobial peptides and proteins, including defensins, histatin 5, lactoferricin, LL-37, lactoferrin, and synthetic antimicrobial peptides such as novispirin G10 (4,6,13,14,19,29,33). Although similar experimental low-salt conditions are not encountered in biological fluids, which brings into question the potential therapeutic application of these compounds, most peptides exhibit antimicrobial activities in vivo (24,27). It will be necessary to perform in vivo assays with Lfpep and kaliocin-1 to determine their potential value as therapeutic agents.…”

Antagonists of Hsp16.3, a Low-Molecular-Weight Mycobacterial Chaperone and Virulence Factor, Derived from Phage-Displayed Peptide Libraries

“…They are both derived from histatins, which are histidine-rich peptides produced by the salivary glands of humans. It has been suggested that histatins may be used to combat Pseudomonas aeruginosa infections in the airways of cystic fibrosis patients (21). It would be interesting to study the effect of histatins on Hsp16.3 on one hand and on mycobacterial viability on the other.…”