title: Membrane Interactions of Natural Cyclic Lipodepsipeptides of the Viscosin Group.
abstract: Many Pseudomonas spp. produce cyclic lipodepsipeptides (CLPs), which, besides their role in biological functions such as motility, biofilm formation and interspecies interactions, are antimicrobial. It has been established that interaction with the cellular membrane is central to the mode of action of CLPs. In this work, we focus on the CLPs of the so-called viscosin group, aiming to assess the impact of the main structural variations observed within this group on both the antimicrobial activity and the interaction with model membranes. The antimicrobial activity of viscosin, viscosinamide A, WLIP and pseudodesmin A were all tested on a broad panel of mainly Gram-positive bacteria. Their capacity to permeabilize or fuse PG/PE/cardiolipin model membrane vesicles is assessed using fluorescent probes. We find that the Glu2/Gln2 structural variation within the viscosin group is the main factor that influences both the membrane permeabilization properties and the minimum inhibitory concentration of bacterial growth, while the configuration of the Leu5 residue has no apparent effect. The CLP-membrane interactions were further evaluated using CD and FT-IR spectroscopy on model membranes consisting of PG/PE/cardiolipin or POPC with or without cholesterol. In contrast to previous studies, we observe no conformational change upon membrane insertion. The CLPs interact both with the polar heads and aliphatic tails of model membrane systems, altering bilayer fluidity, while cholesterol reduces CLP insertion depth.
authors.affiliation: NMR and Structural Analysis Unit, Ghent University;, Belgium.
authors.forename: Niels
authors.initials: N
authors.lastname: Geudens
authors.affiliation: Laboratory of Molecular Biophysics at Interfaces, University of Liège, Gembloux, Belgium.
authors.forename: Mehmet Nail
authors.initials: MN
authors.lastname: Nasir
authors.affiliation: Laboratory of Molecular Biophysics at Interfaces, University of Liège, Gembloux, Belgium.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Crowet
authors.affiliation: Department of Microbial Ecology, Netherlands Institute of Ecology, Wageningen, Netherlands.
authors.forename: Jos M
authors.initials: JM
authors.lastname: Raaijmakers
authors.affiliation: NMR and Structural Analysis Unit, Ghent University;, Belgium.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Fehér
authors.affiliation: Laboratory of Pharmaceutical Microbiology, Ghent University, Belgium.
authors.forename: Tom
authors.initials: T
authors.lastname: Coenye
authors.affiliation: NMR and Structural Analysis Unit, Ghent University;, Belgium.
authors.forename: José C
authors.initials: JC
authors.lastname: Martins
authors.affiliation: Laboratory of Molecular Biophysics at Interfaces, University of Liège, Gembloux, Belgium.
authors.forename: Laurence
authors.initials: L
authors.lastname: Lins
authors.affiliation: NMR and Structural Analysis Unit, Ghent University;, Belgium. Electronic address: davy.sinnaeve@ugent.be.
authors.forename: Davy
authors.initials: D
authors.lastname: Sinnaeve
authors.affiliation: Laboratory of Molecular Biophysics at Interfaces, University of Liège, Gembloux, Belgium. Electronic address: magali.deleu@ulg.ac.be.
authors.forename: Magali
authors.initials: M
authors.lastname: Deleu
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D002942:Circular Dichroism; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D055666:Lipopeptides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D010539:Permeability / Q000187:drug effects; D011549:Pseudomonas / Q000378:metabolism; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D001426:Bacterial Proteins; D008051:Lipid Bilayers; D055666:Lipopeptides; D010456:Peptides, Cyclic; C121478:viscosinamide; C062796:viscosin
keywords: antimicrobial activity; cyclic lipodepsipeptide; membrane permeabilization; model membranes; spectroscopy; viscosin group