title: High in vitro antimicrobial activity of β-peptoid-peptide hybrid oligomers against planktonic and biofilm cultures of Staphylococcus epidermidis.
abstract: An array of β-peptoid-peptide hybrid oligomers displaying different amino acid/peptoid compositions and chain lengths was studied with respect to antimicrobial activity against Staphylococcus epidermidis both in planktonic and biofilm cultures, comparing the effects with those of the common antibiotic vancomycin. Susceptibility and time-kill assays were performed to investigate activity against planktonic cells, whilst confocal laser scanning microscopy was used to investigate the dynamics of the activity against cells within biofilms. All tested peptidomimetics were bactericidal against both exponentially growing and stationary-phase S. epidermidis cells with similar killing kinetics. At the minimum inhibitory concentration (MIC), all peptidomimetics inhibited biofilm formation, whilst peptidomimetics at concentrations above the MIC (80-160μg/mL) eradicated young (6-h-old) biofilms, whilst even higher concentrations were needed to eradicate mature (24-h-old) biofilms completely. Chiral and guanidinylated hybrids exhibited the fastest killing effects against slow-growing cells and had more favourable antibiofilm properties than analogues only containing lysine or lacking chirality in the β-peptoid residues. However, the results of the mature biofilm killing assay indicated more complex structure-activity relationships. Cytotoxicity assays showed a clear correlation between oligomer length and cell toxicity within each subclass of peptides, but all possessed a high differential toxicity favouring killing of bacterial cells. This class of peptidomimetics may constitute promising antimicrobial alternatives for the prevention and treatment of multidrug-resistant S. epidermidis infections.
authors.affiliation: Department of Systems Biology, Technical University of Denmark, Kgs. Lyngby, Denmark.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Kolja M
authors.initials: KM
authors.lastname: Knapp
authors.forename: Liang
authors.initials: L
authors.lastname: Yang
authors.forename: Søren
authors.initials: S
authors.lastname: Molin
authors.forename: Henrik
authors.initials: H
authors.lastname: Franzyk
authors.forename: Anders
authors.initials: A
authors.lastname: Folkesson
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D018441:Biofilms / Q000187:drug effects*; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis; D006801:Humans; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D034444:Peptoids / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D013212:Staphylococcus epidermidis / Q000187:drug effects* / Q000502:physiology*; D013329:Structure-Activity Relationship; D013997:Time Factors; D014640:Vancomycin / Q000494:pharmacology / Q000633:toxicity
chemical_list: D000900:Anti-Bacterial Agents; D010455:Peptides; D034444:Peptoids; D014640:Vancomycin