Identification and optimization of an antimicrobial peptide from the ant venom toxin pilosulin.
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.
Zelezetsky
Igor
I
Department of Biochemistry, Biophysics and Macromolecular Chemistry, University of Trieste, 34127 Trieste, Italy. zelezetsky@bbcm.units.it
Pag
Ulrike
U
Antcheva
Nikolinka
N
Sahl
Hans-Georg
HG
Tossi
Alessandro
A
D000595:Amino Acid Sequence; D000818:Animals; D000862:Ant Venoms / Q000737:chemistry* / Q000378:metabolism*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D001000:Ants; D001419:Bacteria / Q000378:metabolism; D002176:Candida albicans / Q000378:metabolism; D002942:Circular Dichroism; D019992:Databases as Topic; D024881:Drug Resistance, Bacterial; D018432:Drug Resistance, Multiple; D004912:Erythrocytes / Q000378:metabolism / Q000382:microbiology; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013997:Time Factors
D000862:Ant Venoms; D023181:Antimicrobial Cationic Peptides; C115595:pilosulin 1