title: Human beta-defensin 2 and beta-defensin 3 chimeric peptides reveal the structural basis of the pathogen specificity of their parent molecules.
abstract: Despite partial sequence identity and structural similarity, human β-defensin 3 (HBD3) kills Staphylococcus aureus with a 4- to 8-fold higher efficiency than human β-defensin 2 (HBD2), whereas the activities against Escherichia coli are identical. The design and characterization of HBD2/HBD3 chimeric peptides revealed that distinct molecular regions are responsible for their divergent killing properties. Two of the chimeras killed both E. coli and S. aureus with an even higher efficacy than the wild-type molecules. Moreover, one of these two chimeras maintained its high killing activities in the presence of physiologic salt concentrations. Due to the broad spectrum of their antimicrobial activities against many human multidrug-resistant pathogens, these two designer peptides of human origin represent promising templates for a new class of antibiotics.
authors.affiliation: Biochemisches Institut, Christian-Albrechts-Universität zu Kiel, Olshausenstrasse 40, 24118 Kiel, Germany.
authors.forename: Sascha
authors.initials: S
authors.lastname: Jung
authors.forename: Justyna
authors.initials: J
authors.lastname: Mysliwy
authors.forename: Björn
authors.initials: B
authors.lastname: Spudy
authors.forename: Inken
authors.initials: I
authors.lastname: Lorenzen
authors.forename: Karina
authors.initials: K
authors.lastname: Reiss
authors.forename: Christoph
authors.initials: C
authors.lastname: Gelhaus
authors.forename: Rainer
authors.initials: R
authors.lastname: Podschun
authors.forename: Matthias
authors.initials: M
authors.lastname: Leippe
authors.forename: Joachim
authors.initials: J
authors.lastname: Grötzinger
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D004285:Dogs; D004926:Escherichia coli / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D010455:Peptides / Q000138:chemical synthesis / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; C422950:DEFB103A protein, human; C106641:DEFB4A protein, human; D010455:Peptides; D011994:Recombinant Proteins; D023083:beta-Defensins