Web Date: May 29, 2012
Modified Bee Peptide Slays Deadly Bacteria
Researchers have co-opted an antimicrobial peptide made by honeybees and turned it into a potential medicine to treat infections of drug-resistant bacteria (ACS Chem. Biol., DOI: 10.1021/cb300063v).
As more and more bacteria develop resistance, “there is an urgent need for new antibiotics,” says Ralf Hoffmann of the University of Leipzig, in Germany. He thought that peptides used by insects to kill microbes were promising drug candidates because, compared to current antibiotics, they use “a completely different mode of action.” The bee peptides easily slip through bacterial cell membranes and then bind to small proteins that assist with protein folding. By disrupting protein folding, the peptides lead to cell death.
Hoffmann and his colleagues started their search with apidaecin 1b, an 18-amino-acid peptide found in honeybees (Apis mellifera). They found that this peptide easily killed a harmless strain of Escherichia coli. Unfortunately, it was less effective against pathogenic bacteria.
To make apidaecin 1b more toxic to stubborn bacteria, Hoffmann and his colleagues synthesized hundreds of variations of the bee peptide, using both natural and nonnatural amino acids. Api88, the most potent peptide, could kill 37 strains of bacteria, including drug-resistant ones, at concentrations as low as 0.125 µg/mL.
Next, the researchers infected mice with one of two deadly strains of E. coli and then injected api88 into the mice. They found that the peptide cleared the infections at doses of 1.25 and 5 mg per kg of body weight. Hoffmann says the peptides are as potent as conventional antibiotics that treat the strains. Finally, to test the peptide’s toxicity, they injected mice with api88, and looked for signs of unusual behavior or cellular damage. The mice showed no signs of toxicity up to a dose of 40 mg per kg of body weight.
Hoffmann plans to test whether api88 is as effective against resistant bacterial strains in animals as it is in culture.
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