In Vivo Activity of Optimized Apidaecin and Oncocin Peptides Against a Multiresistant, KPC-Producing Klebsiella pneumoniae Strain

Eszter      Ostorhazi; Eva      Nemes-Nikodem; Daniel      Knappe; Ralf      Hoffmann

doi:10.2174/09298665113206660107

Abstract

The peptides Api88 and Onc72 are highly efficient to treat Escherichia coli bacteremia in mice. Here we extended the animal studies to a systemic murine infection model using a multidrug-resistant carbapenemase-producing Klebsiella pneumoniae clinical isolate. When administered intraperitoneally three times at 2.5, 5 and 10 mg/kg bodyweight to CD-1 mice infected with a KPC-producing K. pneumoniae strain, both Api88 and Onc72 reduced the bacterial counts by at least 5 log10 units, indicating that both peptides are active in vivo. Both peptide treatments increased significantly the survival rates and average survival times compared to untreated animals for all doses except for the highest dose of Onc72. This dose reduced the bacterial counts so fast that it most likely induced a sudden release of large amounts of toxic materials from the killed bacteria reducing the survival time even below that of untreated mice. In conclusion, both peptides were efficient in the lethal murine K. pneumoniae infection model, but the treatment protocol (i.e. dose and time points) has to be further optimized based on future pharmacokinetic studies.

Keywords: Antibacterial peptides, Api88, Klebsiella pneumoniae carbapenemase (KPC), murine infection model, Onc72.

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