protegrin-1 and bactenecin

We performed a comparative study of effects of two structurally different cationic antimicrobial peptides of cathelicidin family, porcine protegrin 1 (PG1) and caprine bactenecin 5 (Bac5) on selected tumor and normal mammalian cells in vitro. Protegrins are amphiphilic beta-hairpin molecules having broad-spectrum antimicrobial activity due to their marked membranolytic properties. Bac5 belongs to the group of proline-rich peptides, which adopt a polyproline type II extended helix and kill microorganisms rather by a non-lytic mechanism. We have shown that while PG1 exerts distinct and fast cytotoxic effects on most of used tumor cells being slightly less toxic for nontransformed host cell, the proline-rich Bac5 is much less cytotoxic for all the cells tested. The toxic effects of PG1 were partially declined in the presence of 10% fetal calf serum. It was revealed that PG1 was able to interact with proteins of serpin family (as had been previously established for human defensins by Panyutich et al., 1995). Pre-incubation of PG1 with alpha1-antitrypsin caused the decrease of the cytotoxic activity of the peptide and, on the other hand, the antiprotease activity of alpha1-antitrypsin was reduced after interaction of the serpin with PG1 (not with Bac5). Confocal microscopy experiments allowed to monitor the internalization of fluorescent labeled (by BODIPY FL) peptides into target cells and their intracellular distribution. Bac5-BODIPY (at 5 microM) was rapidly taken into the cells. PG1-BODIPY at non-toxic concentrations was also able to enter the cells without significant damage to them. The comparative study of the kinetics of the peptides uptake into the target cells and the influence of low temperature, energy-depletion and endocytosis inhibitors on the process of the internalization of the peptides into the cells was carried out using flow cytometry.

Topics: Adenosine Triphosphate; alpha 1-Antitrypsin; Animals; Antimicrobial Cationic Peptides; Biological Transport, Active; Cell Line; Cell Line, Tumor; Cold Temperature; Endocytosis; Flow Cytometry; Goats; Humans; Immunity, Innate; Microscopy, Confocal; Neutrophils; Peptides, Cyclic; Proteins; Swine

The in vitro activity of six cathelicidin peptides against 25 strains of Chlamydia was investigated. SMAP-29 proved to be the most active peptide, reducing the inclusion numbers of all 10 strains of Chlamydia trachomatis tested by > or =50% at 10 microg/ml. This peptide was also active against C. pneumoniae and C. felis.

Topics: Antimicrobial Cationic Peptides; Blood Proteins; Cathelicidins; Chlamydia; Chlamydia trachomatis; Chlamydophila pneumoniae; Peptides, Cyclic; Proteins

A single animal can express several cationic antimicrobial peptides with different sequences and structures. We demonstrate that mammalian peptides from different structural classes frequently show synergy with each other and selectively show synergy with human lysozyme.

Topics: Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Drug Synergism; Escherichia coli; Humans; Microbial Sensitivity Tests; Muramidase; Peptides; Peptides, Cyclic; Proteins; Pseudomonas aeruginosa; Staphylococcus aureus