title: Lipid II is an intrinsic component of the pore induced by nisin in bacterial membranes.
abstract: The peptidoglycan layers surrounding bacterial membranes are essential for bacterial cell survival and provide an important target for antibiotics. Many antibiotics have mechanisms of action that involve binding to Lipid II, the prenyl chain-linked donor of the peptidoglycan building blocks. One of these antibiotics, the pore-forming peptide nisin uses Lipid II as a receptor molecule to increase its antimicrobial efficacy dramatically. Nisin is the first example of a targeted membrane-permeabilizing peptide antibiotic. However, it was not known whether Lipid II functions only as a receptor to recruit nisin to bacterial membranes, thus increasing its specificity for bacterial cells, or whether it also plays a role in pore formation. We have developed a new method to produce large amounts of Lipid II and variants thereof so that we can address the role of the lipid-linked disaccharide in the activity of nisin. We show here that Lipid II is not only the receptor for nisin but an intrinsic component of the pore formed by nisin, and we present a new model for the pore complex that includes Lipid II.
authors.affiliation: Center of Biomembranes and Lipid Enzymology, Department of Biochemistry of Membranes, Institute for Biomembranes, University of Utrecht, Padualaan 8 3584 CH Utrecht, The Netherlands. e.j.breukink@chem.uu.nl
authors.forename: Eefjan
authors.initials: E
authors.lastname: Breukink
authors.forename: Hester E
authors.initials: HE
authors.lastname: van Heusden
authors.forename: Pauline J
authors.initials: PJ
authors.lastname: Vollmerhaus
authors.forename: Ewa
authors.initials: E
authors.lastname: Swiezewska
authors.forename: Livia
authors.initials: L
authors.lastname: Brunner
authors.forename: Suzanne
authors.initials: S
authors.lastname: Walker
authors.forename: Albert J R
authors.initials: AJ
authors.lastname: Heck
authors.forename: Ben
authors.initials: B
authors.lastname: de Kruijff
mesh_terms: D008563:Membrane Lipids / Q000302:isolation & purification / Q000378:metabolism*; D009561:Nisin / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D008563:Membrane Lipids; D009561:Nisin