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Báo cáo khoa học: Zinc potentiates the antibacterial effects of histidine-rich peptides against Enterococcus faecalis

Antimicrobial peptides are effector molecules of the innate immune system. We have recently shown that peptides containing multiples of the heparin-binding Cardin and Weintraub motifs AKKARA and ARKKAAKA exert antimicrobial activities. Here, we show that replacement of lysine and arginine in these motifs by histidine abrogates the antibacterial effects of these peptides. | ềFEBS Journal Zinc potentiates the antibacterial effects of histidine-rich peptides against Enterococcus faecalis Victoria Rydengard Emma Andersson Nordahl and Artur Schmidtchen Section of Dermatology and Venereology Department of ClinicalSciences Lund University Sweden Keywords antimicrobialpeptide Enterococcus faecalis heparin high molecular weight kininogen zinc Correspondence V. Rydengard Department of Clinical Sciences Lund University Biomedical Center B14 Tornavagen 10 SE221 84 Lund Sweden Fax 46 46 157 756 Tel 46 46 222 3315 E-mail victoria.rydengard@med.lu.se Received 14 February 2006 revised 21 March 2006 accepted 23 March 2006 doi 10.1111 j.1742-4658.2006.05246.x Antimicrobial peptides are effector molecules of the innate immune system. We have recently shown that peptides containing multiples of the heparin-binding Cardin and Weintraub motifs AKKARA and ARKKAAKA exert antimicrobial activities. Here we show that replacement of lysine and arginine in these motifs by histidine abrogates the antibacterial effects of these peptides. Antibacterial activity of the histidine-rich peptides against the Gram-positive bacterium Enterococcus faecalis was restored by the addition of Zn2 . Fluorescence microscopy experiments showed that Zn2 enabled binding of the histidine-rich peptides to Enterococcus faecalis bacteria. Similar Zn2 -dependent antibacterial activities were shown for hista-tin 5 as well as histidine-containing peptides derived from the Zn2 - and heparin-binding domain 5 of human kininogen. Thus the results demonstrate a previously undisclosed Zn2 -dependent antibacterial activity of kininogen-derived peptides and indicate an important role for Zn2 in regulating the antimicrobial activities of histidine-rich peptides. Antimicrobial substances in blood and leukocytes were discovered over 100 years ago 1 . The identification of antimicrobial peptides AMPs in polymorphonuclear leukocytes 2 was followed by their molecular characterization 3 4 . The .