Identification and optimization of an antimicrobial peptide from the ant venom toxin pilosulin |
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Authors: | Zelezetsky Igor Pag Ulrike Antcheva Nikolinka Sahl Hans-Georg Tossi Alessandro |
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Affiliation: | Department of Biochemistry, Biophysics and Macromolecular Chemistry, University of Trieste, 34127 Trieste, Italy. zelezetsky@bbcm.units.it |
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Abstract: | A template based on positional residue frequencies in the N-terminal stretch of natural alpha-helical antimicrobial peptides was used to prepare sequence patterns and to scan the Swiss-Prot Database, using the ScanProsite tool. This search identified a segment in pilosulin 1, a cytotoxic peptide from the venom of the jumper ant Myrmecia pilosula, as a potential novel antimicrobial peptide sequence. This segment, corresponding to the 20 N-terminal residues, was synthesized and its structural properties and biological activities were investigated. It showed a potent and broad spectrum antimicrobial activity including standard and multi-drug resistant gram-positive and gram-negative bacteria and Candida albicans, confirming the validity of the search method. A rational redesign approach resulting in four amino acid substitutions yielded a variant with improved antibacterial and significantly reduced hemolytic activity. |
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Keywords: | Antimicrobial peptide Sequence template Cytotoxicity Venom Pilosulin |
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