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. 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 histatin 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.
Rydengård
Victoria
V
Section of Dermatology and Venereology, Department of Clinical Sciences, Lund University, Sweden. victoria.rydengard@med.lu.se
Andersson Nordahl
Emma
E
Schmidtchen
Artur
A
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism; D004357:Drug Synergism; D013293:Enterococcus faecalis / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development; D054808:Histatins; D006639:Histidine; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D012471:Salivary Proteins and Peptides / Q000494:pharmacology; D015032:Zinc / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; C068075:HTN3 protein, human; D054808:Histatins; D010455:Peptides; D012471:Salivary Proteins and Peptides; D006639:Histidine; D015032:Zinc