title: Bacterial killing by heparin-binding peptides from PRELP and thrombospondin.
abstract: Antimicrobial peptides (AMP) are effector molecules of the innate immune system. A cross-functionality exists between AMPs and heparin-binding peptides. Here, we show that the peptides QPTRRPRPGTGPGRRPRPRPRP (QPT22), derived from proline arginine-rich end leucine-rich repeat protein (PRELP) and KRFKQDGGWSHWSPWSS (KRF17) from thrombospondin exert antimicrobial activities against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, as well as against the Gram-positive Bacillus subtilis. Analysis by fluorescence microscopy demonstrated that QPT22 and KRF17 bind to bacterial membranes. Particularly QPT22 was found to induce membrane leakage of liposomes. The peptides displayed no hemolytic activities, nor did they exert membrane permeabilising effects on human epithelial cells. Additional peptides derived from heparin-binding regions of laminin, vitronectin, and fibronectin exerted similar antibacterial effects. Several peptides also showed activity against Staphylococcus aureus. Thus, the data disclose a novel antimicrobial activity of heparin-binding regions of matrix glycoproteins. The findings can be utilized in the development of novel AMPs for therapeutic use.
authors.affiliation: Department of Pharmacy, Uppsala University, SE-751 23 Uppsala, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Malmsten
authors.forename: Mina
authors.initials: M
authors.lastname: Davoudi
authors.forename: Artur
authors.initials: A
authors.lastname: Schmidtchen
mesh_terms: D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects; D001419:Bacteria / Q000187:drug effects*; D001798:Blood Proteins / Q000737:chemistry*; D002352:Carrier Proteins / Q000737:chemistry*; D004926:Escherichia coli / Q000187:drug effects; D005109:Extracellular Matrix / Q000737:chemistry; D016326:Extracellular Matrix Proteins / Q000737:chemistry*; D006023:Glycoproteins / Q000737:chemistry*; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D019699:Thrombospondins / Q000737:chemistry*
chemical_list: C062991:AZU1 protein, human; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D002352:Carrier Proteins; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; C096382:PRELP protein, human; D010446:Peptide Fragments; D019699:Thrombospondins