magainin-2-peptide--xenopus and Bacterial-Infections

The therapy of bacterial infections is currently a difficult problem of the contemporary medicine, mainly due to the increasing spread of resistance to conventional antibiotics and to the appearance of multi-resistant bacterial strains. Although the gene-encoded antimicrobial peptides were described for a while their intensive research and study of their possible clinical applications has started only in the recent years. These antimicrobial peptides appear to form part of the most ancient defense mechanisms of the phylogenesis by exerting cytotoxic (mainly membrane damaging) effects against many bacteria. In this review the author attempts to make a brief synopsis--from a medical point of view--of the most important antimicrobial peptides and their possible clinical applications.

Topics: Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Bacterial Infections; Drug Resistance, Microbial; Humans; Magainins; Xenopus Proteins

The histidine-rich amphipathic cationic peptide LAH4 has antibiotic and DNA delivery capabilities. Here, we explore the interaction of peptides from this family with model membranes as monitored by solid-state (2)H nuclear magnetic resonance and their antibiotic activities against a range of bacteria. At neutral pH, the membrane disruption is weak, but at acidic pH, the peptides strongly disturb the anionic lipid component of bacterial membranes and cause bacterial lysis. The peptides are effective antibiotics at both pH 7.2 and pH 5.5, although the antibacterial activity is strongly affected by the change in pH. At neutral pH, the LAH peptides were active against both methicillin-resistant and -sensitive Staphylococcus aureus strains but ineffective against Pseudomonas aeruginosa. In contrast, the LAH peptides were highly active against P. aeruginosa in an acidic environment, as is found in the epithelial-lining fluid of cystic fibrosis patients. Our results show that modest antibiotic activity of histidine-rich peptides can be dramatically enhanced by inducing membrane disruption, in this case by lowering the pH, and that histidine-rich peptides have potential as future antibiotic agents.

Topics: Amino Acid Sequence; Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Bacterial Infections; Cell Membrane; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Hydrogen-Ion Concentration; Magainins; Magnetic Resonance Spectroscopy; Microbial Sensitivity Tests; Molecular Sequence Data; Peptides; Xenopus; Xenopus Proteins

The ability of magainin 2 to augment antibiotic therapy was examined. Susceptibility to magainin 2 was determined on Escherichia coli incubated in the presence and absence of sublethal concentrations of antibiotics both in vitro and in vivo. Experiments in buffer and normal human serum revealed that E. coli exposed to sublethal amounts of cefepime, a beta-lactam antibiotic, was significantly more susceptible to the antimicrobial activity of magainin 2. Bacteria incubated with subinhibitory concentrations of other beta-lactam type antibiotics, but not amikacin (an aminoglycoside) or ciprofloxacin (a quinolone), were also more susceptible to magainin 2 in normal human serum. Bacteria were less susceptible to magainin 2 when they were examined in heat-inactivated serum. Complement was shown to be required for magainin 2 activity in serum by using C8-deficient sera. The combination of magainin 2 and cefepime was shown to be more antimicrobial in normal human serum for a variety of bacterial strains. Magainin 2 was completely inactive as a therapeutic agent when it was administered alone (2 mg per mouse) but significantly increased the survival of mice when it was administered with a low level of cefepime.

Topics: Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Bacteria; Bacterial Infections; Cefepime; Cephalosporins; Drug Evaluation, Preclinical; Drug Synergism; Escherichia coli; Magainins; Male; Mice; Microbial Sensitivity Tests; Peptides; Xenopus Proteins