title: Lipid II-based antimicrobial activity of the lantibiotic plantaricin C.
abstract: We analyzed the mode of action of the lantibiotic plantaricin C (PlnC), produced by Lactobacillus plantarum LL441. Compared to the well-characterized type A lantibiotic nisin and type B lantibiotic mersacidin, which are both able to interact with the cell wall precursor lipid II, PlnC displays structural features of both prototypes. In this regard, we found that lipid II plays a key role in the antimicrobial activity of PlnC besides that of pore formation. The pore forming activity of PlnC in whole cells was prevented by shielding lipid II on the cell surface. However, in contrast to nisin, PlnC was not able to permeabilize Lactococcus lactis cells or to form pores in 1,2-dioleoyl-sn-glycero-3-phosphocholine liposomes supplemented with 0.1 mol% purified lipid II. This emphasized the different requirements of these lantibiotics for pore formation. Using cell wall synthesis assays, we identified PlnC as a potent inhibitor of (i) lipid II synthesis and (ii) the FemX reaction, i.e., the addition of the first Gly to the pentapeptide side chain of lipid II. As revealed by thin-layer chromatography, both reactions were clearly blocked by the formation of a PlnC-lipid I and/or PlnC-lipid II complex. On the basis of the in vivo and in vitro activities of PlnC shown in this study and the structural lipid II binding motifs described for other lantibiotics, the specific interaction of PlnC with lipid II is discussed.
authors.affiliation: Institut für Medizinische Mikrobiologie une Immunologie-Pharmazeutische Mikrobiologie, Universität Bonn, D-53115 Bonn, Germany.
authors.forename: Imke
authors.initials: I
authors.lastname: Wiedemann
authors.forename: Tim
authors.initials: T
authors.lastname: Böttiger
authors.forename: Raquel Regina
authors.initials: RR
authors.lastname: Bonelli
authors.forename: Tanja
authors.initials: T
authors.lastname: Schneider
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Sahl
authors.forename: Beatriz
authors.initials: B
authors.lastname: Martínez
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001430:Bacteriocins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002473:Cell Wall / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D013294:Lactococcus lactis / Q000187:drug effects*; D008081:Liposomes; D008826:Microbial Sensitivity Tests; D008837:Micrococcus / Q000187:drug effects*; D009561:Nisin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D010457:Peptidoglycan / Q000096:biosynthesis; D013329:Structure-Activity Relationship; D014538:Uridine Diphosphate N-Acetylmuramic Acid / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D008081:Liposomes; D010455:Peptides; D010457:Peptidoglycan; D014538:Uridine Diphosphate N-Acetylmuramic Acid; C069249:muramyl-NAc-(pentapeptide)pyrophosphoryl-undecaprenol; C089260:plantaricin C; C069959:mersacidin; D009561:Nisin