title: Structure and mode of action of cyclic lipopeptide pseudofactin II with divalent metal ions.
abstract: The interaction of natural lipopeptide pseudofactin II with a series of doubly charged metal cations was examined by matrix-assisted laser-desorption ionization-time of flight (MALDI-TOF) mass spectrometry and molecular modelling. The molecular modelling for metal-pseudofactin II provides information on the metal-peptide binding sites. Overall, Mg(2+), Ca(2+) and Zn(2+) favor the association with oxygen atoms spanning the peptide backbone, whereas Cu(2+) is coordinated by three nitrogens. Circular dichroism (CD) results confirmed that Zn(2+) and Cu(2+) can disrupt the secondary structure of pseudofactin II at high concentrations, while Ca(2+) and Mg(2+) did not essentially affect the structure of the lipopeptide. Interestingly, our results showed that the addition of Zn(2+) and Cu(2+) helped smaller micelles to form larger micellar aggregates. Since pseudofactin II binds metals, we tested whether this phenomena was somehow related to its antimicrobial activity against Staphylococcus epidermidis and Proteus mirabilis. We found that the antimicrobial effect of pseudofactin II was increased by supplementation of culture media with all tested divalent metal ions. Finally, by using Gram-positive and Gram-negative bacteria we showed that the higher antimicrobial activity of metal complexes of pseudofactin II is attributed to the disruption of the cytoplasmic membrane.
authors.affiliation: Department of Inorganic Chemistry, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211a, 50-556 Wroclaw, Poland. Electronic address: tomasz.janek@umed.wroc.pl.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Janek
authors.affiliation: Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
authors.forename: Lígia R
authors.initials: LR
authors.lastname: Rodrigues
authors.affiliation: Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
authors.forename: Eduardo J
authors.initials: EJ
authors.lastname: Gudiña
authors.affiliation: Department of Inorganic Chemistry, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211a, 50-556 Wroclaw, Poland.
authors.forename: Żaneta
authors.initials: Ż
authors.lastname: Czyżnikowska
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D002413:Cations, Divalent / Q000737:chemistry* / Q000378:metabolism; D002942:Circular Dichroism; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D055666:Lipopeptides / Q000737:chemistry* / Q000494:pharmacology*; D013058:Mass Spectrometry; D008670:Metals / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular
chemical_list: D000900:Anti-Bacterial Agents; D002413:Cations, Divalent; D055666:Lipopeptides; D008670:Metals
keywords: Circular dichroism; Lipopeptides; Metal-ion interaction; Molecular modelling; Pseudofactin II; Uropathogenic microorganisms