title: Peptides derived from the human laminin alpha4 and alpha5 chains exhibit antimicrobial activity.
abstract: Laminins are a family of heterotrimeric extracellular matrix glycoproteins in the basement membrane of different tissues and are composed of alpha, beta, and gamma chains. In mammals, five different alpha chains, three beta chains, and three gamma chains have been identified that assemble into 15 different laminins. Each alpha-chain possesses a C-terminal globular domain which can be subdivided into the five subdomains LG1-LG5. LG1-LG3 modules are connected to LG4-LG5 by a linker domain which is known to be sensitive to proteolytic processing. Here, we show that peptides derived from the human laminin alpha4 and alpha5 chain, exhibit a dose-dependent antimicrobial activity against gram-positive and gram-negative bacteria. Furthermore, we show that these peptides permeabilize the bacterial membrane and are able to bind to bacterial DNA. Interestingly, the ability to kill the microorganisms correlated with their ability to bind to heparin. These data suggest that extracellular matrix components are able to protect the respective tissues from invading pathogens and are part of the host defense response.
authors.affiliation: Department of Dermatology, University of Tübingen, Germany. ilknur.senyuerek@med.uni-tuebingen.de
authors.forename: Ilknur
authors.initials: I
authors.lastname: Senyürek
authors.forename: Gerd
authors.initials: G
authors.lastname: Klein
authors.forename: Hubert
authors.initials: H
authors.lastname: Kalbacher
authors.forename: Martin
authors.initials: M
authors.lastname: Deeg
authors.forename: Birgit
authors.initials: B
authors.lastname: Schittek
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D015169:Colony Count, Microbial; D004269:DNA, Bacterial / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D048168:Escherichia coli K12 / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D006461:Hemolysis / Q000187:drug effects; D006493:Heparin / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D007797:Laminin / Q000737:chemistry / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D018613:Microscopy, Confocal; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology*; D054730:Protein Interaction Domains and Motifs; D013211:Staphylococcus aureus / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D004269:DNA, Bacterial; C501369:LAMA4 protein, human; D007797:Laminin; D010446:Peptide Fragments; C097043:laminin alpha5; D006493:Heparin