title: Short cationic lipopeptides as effective antibacterial agents: Design, physicochemical properties and biological evaluation.
abstract: The spread of drug-resistant bacteria has imparted a sense of urgency in the search for new antibiotics. In an effort to develop a new generation of antibacterial agents, we have designed de novo charged lipopeptides inspired by natural antimicrobial peptides. These short lipopeptides are composed of cationic lysine and hydrophobic lipoamino acids that replicate the amphiphilic properties of natural antimicrobial peptides. The resultant lipopeptides were found to self-assemble into nanoparticles. Some were effective against a variety of Gram-positive bacteria, including strains resistant to methicillin, daptomycin and/or vancomycin. The lipopeptides were not toxic to human kidney and liver cell lines and were highly resistant to tryptic degradation. Transmission electron microscopy analysis of bacteria cells treated with lipopeptide showed membrane-damage and lysis with extrusion of cytosolic contents. With such properties in mind, these lipopeptides have the potential to be developed as new antibacterial agents against drug-resistant Gram-positive bacteria.
authors.affiliation: The University of Queensland, School of Chemistry and Molecular Biosciences, St Lucia, Qld 4072, Australia; National University of Malaysia, Faculty of Pharmacy, Kuala Lumpur 50300, Malaysia.
authors.forename: Fazren
authors.initials: F
authors.lastname: Azmi
authors.affiliation: The University of Queensland, Institute for Molecular Bioscience, St Lucia 4072, Australia.
authors.forename: Alysha G
authors.initials: AG
authors.lastname: Elliott
authors.affiliation: The University of Queensland, School of Chemistry and Molecular Biosciences, St Lucia, Qld 4072, Australia.
authors.forename: Nirmal
authors.initials: N
authors.lastname: Marasini
authors.affiliation: The University of Queensland, Institute for Molecular Bioscience, St Lucia 4072, Australia.
authors.forename: Soumya
authors.initials: S
authors.lastname: Ramu
authors.affiliation: The University of Queensland, Institute for Molecular Bioscience, St Lucia 4072, Australia.
authors.forename: Zyta
authors.initials: Z
authors.lastname: Ziora
authors.affiliation: The University of Queensland, Institute for Molecular Bioscience, St Lucia 4072, Australia.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Kavanagh
authors.affiliation: The University of Queensland, Institute for Molecular Bioscience, St Lucia 4072, Australia.
authors.forename: Mark A T
authors.initials: MA
authors.lastname: Blaskovich
authors.affiliation: The University of Queensland, Institute for Molecular Bioscience, St Lucia 4072, Australia.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Cooper
authors.affiliation: The University of Queensland, School of Chemistry and Molecular Biosciences, St Lucia, Qld 4072, Australia.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Skwarczynski
authors.affiliation: The University of Queensland, School of Chemistry and Molecular Biosciences, St Lucia, Qld 4072, Australia; The University of Queensland, Institute for Molecular Bioscience, St Lucia 4072, Australia; The University of Queensland, School of Pharmacy, Brisbane, Qld 4072, Australia. Electronic address: i.toth@uq.edu.au.
authors.forename: Istvan
authors.initials: I
authors.lastname: Toth
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D015195:Drug Design; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy; D006801:Humans; D055666:Lipopeptides / Q000737:chemistry* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests
chemical_list: D000900:Anti-Bacterial Agents; D055666:Lipopeptides
keywords: Amphiphilic; Antibacterial; Lipopeptide; Nanoparticle; Peptidomimetics