title: Synthetic peptides derived from human antimicrobial peptide ubiquicidin accumulate at sites of infections and eradicate (multi-drug resistant) Staphylococcus aureus in mice.
abstract: The presence and antimicrobial activity of antimicrobial peptides (AMPs) has been widely recognized as an evolutionary preserved part of the innate immune system. Based on evidence in animal models and humans, AMPs are now positioned as novel anti-infective agents. The current study aimed to evaluate the potential antimicrobial activity of ubiquicidin and small synthetic fragments thereof towards methicillin resistant Staphylococcus aureus (MRSA), as a high priority target for novel antibiotics. In vitro killing of MRSA by synthetic peptides derived from the alpha-helix or beta-sheet domains of the human cationic peptide ubiquicidin (UBI 1-59), allowed selection of AMPs for possible treatment of MRSA infections. The strongest antibacterial activity was observed for the entire peptide UBI 1-59 and for synthetic fragments comprising amino acids 31-38. The availability, chemical synthesis opportunities, and size of these small peptides, combined with their strong antimicrobial activity towards MRSA make these compounds promising candidates for antimicrobial therapy and detection of infections in man.
authors.affiliation: AM-Pharma, Bunnik, The Netherlands.
authors.forename: Carlo P J M
authors.initials: CP
authors.lastname: Brouwer
authors.forename: Sylvia J P
authors.initials: SJ
authors.lastname: Bogaards
authors.forename: Marty
authors.initials: M
authors.lastname: Wulferink
authors.forename: Markwin P
authors.initials: MP
authors.lastname: Velders
authors.forename: Mick M
authors.initials: MM
authors.lastname: Welling
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology; D004195:Disease Models, Animal; D024901:Drug Resistance, Multiple, Bacterial; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D012269:Ribosomal Proteins / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000188:drug therapy*; D013211:Staphylococcus aureus / Q000187:drug effects*; D013667:Technetium
chemical_list: D000890:Anti-Infective Agents; D010455:Peptides; D012269:Ribosomal Proteins; C040469:ribosomal protein S30; D013667:Technetium