Histidine-rich glycoprotein exerts antibacterial activity.
Histidine-rich glycoprotein (HRGP), an abundant heparin-binding protein found in plasma and thrombocytes, exerts antibacterial effects against Gram-positive bacteria (Enterococcus faecalis and Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Fluorescence studies and electron microscopy to assess membrane permeation showed that HRGP induces lysis of E. faecalisbacteria in the presence of Zn2+ or at low pH. Heparin blocked binding of the protein to E. faecalis and abolished antibacterial activity. Furthermore, truncated HRGP, devoid of the heparin-binding and histidine-rich domain, was not antibacterial. It has previously been shown that peptides containing consensus heparin-binding sequences (Cardin and Weintraub motifs) are antibacterial. Thus, the peptide (GHHPH)4, derived from the histidine-rich region of HRGP and containing such a heparin-binding motif, was antibacterial for E. faecalis in the presence of Zn2+ or at low pH. The results show a previously undisclosed antibacterial activity of HRGP and suggest that the histidine-rich and heparin-binding domain of HRGP mediates the antibacterial activity of the protein.
Rydengård
Victoria
V
Section of Dermatology and Venereology, Lund University, Sweden. victoria.rydengard@med.lu.se
Olsson
Anna-Karin
AK
Mörgelin
Matthias
M
Schmidtchen
Artur
A
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry*; D013293:Enterococcus faecalis / Q000378:metabolism*; D006493:Heparin / Q000737:chemistry; D006639:Histidine / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D015032:Zinc / Q000737:chemistry; D000099053:Histidine-Rich Glycoprotein
D000890:Anti-Infective Agents; D010455:Peptides; D011506:Proteins; D000099053:Histidine-Rich Glycoprotein; D006639:Histidine; D006493:Heparin; D015032:Zinc