• Amphipathic Barbiturates as Mimics of Antimicrobial Peptides and the Marine Natural Products Eusynstyelamides with Activity against Multi-resistant Clinical Isolates 

      Paulsen, Marianne Hagensen; Engqvist, Magnus; Ausbacher, Dominik; Anderssen, Trude; Langer, Manuel Karl; Haug, Tor; Morello, Glenn Robert; Liikanen, Laura; Blencke, Hans-Matti; Isaksson, Johan; Juskewitz, Eric; Bayer, Annette; Strøm, Morten B. (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-07-27)
      We report a series of synthetic cationic amphipathic barbiturates inspired by the pharmacophore model of small antimicrobial peptides (AMPs) and the marine antimicrobials eusynstyelamides. These N,N′-dialkylated-5,5-disubstituted barbiturates consist of an achiral barbiturate scaffold with two cationic groups and two lipophilic side chains. Minimum inhibitory concentrations of 2–8 μg/mL were achieved ...
    • Anti-Colonization Effect of Au Surfaces with Self-Assembled Molecular Monolayers Functionalized with Antimicrobial Peptides on S. epidermidis 

      Karlsen, Eskil André; Stensen, Wenche; Juskewitz, Eric; Svenson, Johan; Berglin, Mattias; Svendsen, John Sigurd Mjøen (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-12-10)
      Medical devices with an effective anti-colonization surface are important tools for combatting healthcare-associated infections. Here, we investigated the anti-colonization efficacy of antimicrobial peptides covalently attached to a gold model surface. The gold surface was modified by a self-assembled polyethylene glycol monolayer with an acetylene terminus. The peptides were covalently connected ...
    • Antimicrobial activity and mode of action - Examples from natural products, peptides, and peptidomimetics 

      Juskewitz, Eric (Doctoral thesis; Doktorgradsavhandling, 2022-08-12)
      Infections caused by bacteria are the third leading cause of death worldwide. Antimicrobials are used to treat and prevent those infections and enabled the development of the modern healthcare system as we know it. However, those achievements are threatened by the global emergence of antimicrobial-resistant bacteria. There is an obvious need for developing new antimicrobials. Natural environments, ...
    • Goldilocks Dilemma: LPS Works Both as the Initial Target and a Barrier for the Antimicrobial Action of Cationic AMPs on E. coli 

      Jakubec, Martin; Rylandsholm, Fredrik G.; Rainsford, Philip; Silk, Mitchell; Bril'kov, Maxim; Kristoffersen, Tone; Juskewitz, Eric; Ericson, Johanna U; Svendsen, John Sigurd Mjøen (Journal article; Tidsskriftartikkel, 2023-07-20)
      Antimicrobial peptides (AMPs) are generally membrane-active compounds that physically disrupt bacterial membranes. Despite extensive research, the precise mode of action of AMPs is still a topic of great debate. This work demonstrates that the initial interaction between the Gram-negative E. coli and AMPs is driven by lipopolysaccharides (LPS) that act as kinetic barriers for the binding of AMPs to ...
    • Label-free measurement of antimicrobial peptide interactions with lipid vesicles and nanodiscs using microscale thermophoresis 

      Rainsford, Philip; Rylandsholm, Fredrik G.; Jakubec, Martin; Silk, Mitchell; Juskewitz, Eric; Ericson, Johanna U; Svendsen, John Sigurd Mjøen; Engh, Richard Alan; Isaksson, Johan Mattias (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-08-03)
      One strategy to combat antimicrobial resistance is the discovery of new classes of antibiotics. Most antibiotics will at some point interact with the bacterial membrane to either interfere with its integrity or to cross it. Reliable and efficient tools for determining the dissociation constant for membrane binding (K<sub>D</sub>) and the partitioning coefficient between the aqueous- and membrane ...
    • Label-free measurement of antimicrobial peptide interactions with lipid vesicles and nanodiscs using microscale thermophoresis 

      Rainsford, Philip Ben; Rylandsholm, Fredrik G.; Jakubec, Martin; Silk, Mitchell; Juskewitz, Eric; Ericson, Johanna Ulrica; Svendsen, John Sigurd Mjøen; Engh, Richard Alan; Isaksson, Johan Mattias (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-08-03)
      One strategy to combat antimicrobial resistance is the discovery of new classes of antibiotics. Most antibiotics will at some point interact with the bacterial membrane to either interfere with its integrity or to cross it. Reliable and efficient tools for determining the dissociation constant for membrane binding (K<sub><i>D</sub></i>) and the partitioning coefficient between the aqueous- and ...
    • Lulworthinone, a New Dimeric Naphthopyrone From a Marine Fungus in the Family Lulworthiaceae With Antibacterial Activity Against Clinical Methicillin-Resistant Staphylococcus aureus Isolates 

      Jenssen, Marte; Rainsford, Philip; Juskewitz, Eric; Andersen, Jeanette Hammer; Hansen, Espen; Isaksson, Johan; Rämä, Teppo; Østnes Hansen, Kine (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-10-01)
      The emergence of drug-resistant bacteria is increasing rapidly in all parts of the world, and the need for new antibiotics is urgent. In our continuous search for new antimicrobial molecules from under-investigated Arctic marine microorganisms, a marine fungus belonging to the family Lulworthiaceae (Lulworthiales, Sordariomycetes, and Ascomycota) was studied. The fungus was isolated from driftwood, ...
    • Lulworthinone: In Vitro Mode of Action Investigation of an Antibacterial Dimeric Naphthopyrone Isolated from a Marine Fungus 

      Juskewitz, Eric; Mishchenko, Ekaterina; Dubey, Vishesh Kumar; Jenssen, Marte; Jakubec, Martin; Rainsford, Philip; Isaksson, Johan Mattias; Andersen, Jeanette Hammer; Ericson, Johanna U (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-04-21)
      Treatment options for infections caused by antimicrobial-resistant bacteria are rendered ineffective, and drug alternatives are needed—either from new chemical classes or drugs with new modes of action. Historically, natural products have been important contributors to drug discovery. In a recent study, the dimeric naphthopyrone lulworthinone produced by an obligate marine fungus in the family ...