Abstract
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.
Highlights
The ability of magainin 2 to augment antibiotic therapy was examined
One effect that we have recently shown is that the serum susceptibility of Pseudomonas aeruginosa is significantly increased when cells were incubated in serum with sublethal concentrations of cefepime, a P-lactam-type antibiotic [5]
The analysis showed that the terminal complement complex was necessary for enhanced antibiotic killing and that the f-lactamaltered bacterial cell surface allowed more terminal complement complex deposition [5]
Summary
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. We are attempting to improve the clinical response to antibiotic treatment for neutropenic patients by investigating therapies that would kill antibiotic-injured bacteria. A group of novel oligopeptide antibiotics which act at the inner bacterial membrane has been described recently [19, 37] These peptides are obtained from a wide variety of different sources and include magainins [39], cecropins [30], sarcotoxins [26], and other similar peptides [2, 10]. The cationic peptides mentioned above demonstrate a selective toxicity for bacteria [3, 23] These peptides represent novel agents for the treatment of systemic bacterial infections. Their in vitro activities are highly susceptible to assay conditions [6], making it difficult to determine whether their potencies are sufficient for in vivo use
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
