Evaluation of the synergistic antibacterial activity of polymyxin b and melittin.

摘要

Melittin is an antibacterial peptide found in honey bee venom. An evaluation was performed to determine if the antibacterial synergy that was observed in vitro between melittin and the antibiotic polymyxin B against E. coli had any effectiveness in vivo.; To determine Polymyxin B--melittin synergy in vivo, a sub-lethal murine septicemia was established using Escherichia coli. Results were evaluated by quantitative plating of blood samples taken by heart puncture. In this infection model, melittin doses of greater than 1 microgram per mouse usually enhanced the establishment of the E. coli infection. It was found, however, that lower doses of melittin, approximately 50 nanograms per mouse, were synergistic with polymyxin B as an antibacterial agent in the murine system.; In vitro assays of succinate-dependent oxygen consumption in E. coli indicated that lower concentrations of melittin which were not effective alone in limiting inner membrane respiration in the bacteria, had such activity in the presence of Polymyxin B. These results demonstrated similarities between the membrane activities of melittin and the C9 component of human complement.; The antibacterial synergy and lytic activity of certain melittin analogs were evaluated to determine if a less lytic peptide could be designed which would still be synergistic with antibiotics. Mastoparan, a vespid venom peptide and a natural melittin analog, demonstrated antibacterial synergy equal to that of melittin, but had less than 5% of the lytic activity.; Based on these results, it was concluded that although synergy between melittin and polymyxin B can be detected in vivo, such activity will not be useful in the treatment of disease until the mechanism whereby melittin sometimes enhanced the establishment of infection is better understood.; An incidental finding in the development of the murine septicemia model showed relative humidity to be an important experimental variable which can affect the susceptibility of mice to infection with E. coli.