Antimicrobial activity of apidaecin peptides
Abstract number: 1733_1580
Czihal P., Nimptsch A., Möllmann U., Zipfel P., Hoffmann R.
In recent years there was a dramatical increase in bacteria strains resistance to one or even several antibiotics. Thus, the development of antimicrobial compounds with novel modes of action is a major focus of current pharmaceutical research. A very interesting and promising approach relies on antibacterial peptides, because bacteria do not develop any resistance to these antimicrobial peptide families. One of the most promising among these families are the short, proline-rich antibacterial peptides originally isolated from insects, such as apidaecin, drosocin, formaecin, and pyrrhocoricin. These peptides represent a viable treatment option for the major pathogens in urinary tract infections, that is, E. coli and K. pneumoniae, causing 9095% of all urinary tract infections.
Based on the native sequences of apidaecin 1a and apidaecin 1b, we have identified all residues important for the antibacterial activity with an alanine scan. In a second round, the identified positions were selectively modified with other alpha-amino acids and unnatural amino acid derivatives to increase the antibacterial activity. Furthermore, the protease resistance was increased to elongate the peptide activity in blood. All peptides were synthesized on solid-phase using the Fmoc/tBu-strategy and purified by reversed phase HPLC. The activities of the peptides were determined by an agar diffusion assay and the minimal inhibition concentration (MIC) was determined on a microtiter plate for pathogenic E. coli strains (e.g. E. coli 1103) and Klebsiella pneumoniae ssp. pneumoniae 11678. The first results on the antimicrobial activities and protease resistances of the new apidaecin analogs will be presented.
|Session name:||European Society of Clinical Microbiology and Infectious Diseases|
|Location:||ICC, Munich, Germany|
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