tailieunhanh - Báo cáo khoa học: 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 faecalisand Staphylococcus aureus) and Gram-negative bacteria (Escherichia coliandPseudomonas aeruginosa). Fluorescence studies and electron microscopy to assess membrane permea-tion showed that HRGP induces lysis of E. | ỊFEBS Journal Histidine-rich glycoprotein exerts antibacterial activity Victoria Rydengard1 Anna-Karin Olsson2 Matthias Morgelin3 and Artur Schmidtchen1 1 Section of Dermatology and Venereology Lund University Sweden 2 Department of Genetics and Pathology Uppsala University Sweden 3 Section of Clinicaland ExperimentalInfectious Medicine Lund University Sweden Keywords antibacterial heparin histidine-rich glycoprotein pH zinc Correspondence V. Rydengard Department of Clinical Sciences Lund University Biomedical Center B14 Tornavagen 10 S-221 84 Lund Sweden Fax 46 46 157756 Tel 46 46 2223315 E-mail Received 11 October 2006 revised 7 November 2006 accepted 9 November 2006 doi 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. faecalis bacteria 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. fae-calis 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. Histidine-rich glycoprotein HRGP is an abundant 67 kDa plasma glycoprotein identified