Beta-lactam antibiotics potentiate magainin 2 antimicrobial activity in vitro and in vivo

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.

Efficacy of Cryptdin-2 as an Adjunct to Antibiotics from Various Generations Against Salmonella

“…These two mechanisms might have acted mutually leading to make this very combination to be the most effective amongst all the combinations tested. These observations are consistent with previous studies pertaining to the synergetic actions of a-helical peptide p18, reproductive tract beta-defensins, HNP-1, magainin, cathelicidins and several other novel cationic peptides with commonly used antibiotics against Escherichia coli, Mycobacterium tuberculosis, Pseudomonas aeruginosa, Klebsiella pneumoniae and Enterobacter cloacae [26,27].…”

IncreasedStaphylococcus-killing Activity of an Antimicrobial Peptide, Lactoferricin B, with Minocycline and Monoacylglycerol

“…LFcin B was prepared as described previously 5) and its purity was at least 95z by HPLC. The following antibiotics were used: methicillin sodium (Banyu Pharmaceutical Co., Tokyo, Japan), ceftizoxime sodium (Fujisawa Pharmaceutical Co., Osaka, Japan), a mixture of 40z S. aureus strains.…”

“…4) As an example of the latter approach, various antimicrobial peptides have been investigated in combination with several conventional antibiotics. [5][6][7][8] Lactoferricin B (LFcin B) and lactoferricin H (LFcin H) are 25-and 47-residue cationic antimicrobial peptides generated by pepsin digestion of bovine lactoferrin (LF) and human LF, respectively. 9) LFcin B has activity against a wide range of microorganisms, including bacteria and fungi, [10][11][12] and the therapeutic e‹cacy of LFcin analogs has been found in several murine models of infection.…”

Peptides related to the carboxyl terminus of human platelet factor IV with antibacterial activity.

“…The data suggested that ,B-lactam-altered bacteria might be more susceptible to other agents, which in a mechanism similar to complement, need to gain access to the bacterial inner membrane for bactericidal activity. To test this hypothesis, the susceptibility of,B-lactam-altered Escherichia coli to a recently described ( 13) antimicrobial peptide designated magainin 2 was examined ( 14). It was demonstrated that ,B-lactam-altered bacteria were significantly more susceptible to magainin 2 both in vitro and in vivo mouse protection experiments.…”