title: Bioactivity of Natural and Engineered Antimicrobial Peptides from Venom of the Scorpions Urodacus yaschenkoi and U. manicatus.
abstract: The spread of multidrug-resistant human pathogens has drawn attention towards antimicrobial peptides (AMPs), which are major players in the innate immune systems of many organisms, including vertebrates, invertebrates, plants and microbes. Scorpion venom is an abundant source of novel and potent AMPs. Here, we investigated natural and engineered AMPs from the scorpionsUrodacus yaschenkoiandU. manicatusto determine their antimicrobial spectra as well as their hemolytic/cytotoxic activity. None of the AMPs were active against fungi, but many of them were active at low concentrations (0.25-30 µM) against seven different bacteria. Hemolytic and cytotoxic activities were determined using pig erythrocytes and baby hamster kidney cells, respectively. The amino acid substitutions in the engineered AMPs did not inhibit cytotoxicity, but reduced hemolysis and therefore increased the therapeutic indices. The phylogenetic analysis of scorpion AMPs revealed they are closely related and the GXK motif is highly conserved. The engineered scorpion AMPs offer a promising alternative for the treatment of multidrug-resistant bacterial infections and could be modified further to reduce their hemolytic/cytotoxic activity.
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology, Winchester Strasse 2, D-35394 Giessen, Germany. karenlunarmrz@gmail.com.
authors.forename: Karen
authors.initials: K
authors.lastname: Luna-Ramirez
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology, Winchester Strasse 2, D-35394 Giessen, Germany. miray.tonk@ime.fraunhofer.de.
authors.forename: Miray
authors.initials: M
authors.lastname: Tonk
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology, Winchester Strasse 2, D-35394 Giessen, Germany. mohammad.rahnamaeian@ime.fraunhofer.de.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Rahnamaeian
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology, Winchester Strasse 2, D-35394 Giessen, Germany. andreas.vilcinskas@agrar.uni-giessen.de.|Institute for Insect Biotechnology, Justus Liebig University of Giessen, D-35392 Giessen, Germany. andreas.vilcinskas@agrar.uni-giessen.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Vilcinskas
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D060829:Arthropod Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D001419:Bacteria / Q000187:drug effects* / Q000254:growth & development; D002460:Cell Line; D006224:Cricetinae; D006461:Hemolysis / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D010802:Phylogeny; D015202:Protein Engineering; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D012604:Scorpion Venoms / Q000235:genetics / Q000378:metabolism*; D012605:Scorpions / Q000235:genetics / Q000378:metabolism*; D034421:Sus scrofa
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D060829:Arthropod Proteins; D011994:Recombinant Proteins; D012604:Scorpion Venoms
keywords: antimicrobial peptides; hemolysis; scorpions; therapeutic index; venom