Antimicrobial Activity of Human Prion Protein Is Mediated by Its N-Terminal Region

BACKGROUND: Cellular prion-related protein (PrP(c)) is a cell-surface protein that is ubiquitously expressed in the human body. The multifunctionality of PrP(c), and presence of an exposed cationic and heparin-binding N-terminus, a feature characterizing many antimicrobial peptides, made us hypothesize that PrP(c) could exert antimicrobial activity. METHODOLOGY AND PRINCIPAL FINDINGS: Intact recombinant PrP exerted antibacterial and antifungal effects at normal and low pH. Studies employing recombinant PrP and N- and C-terminally truncated variants, as well as overlapping peptide 20mers, demonstrated that the antimicrobial activity is mediated by the unstructured N-terminal part of the protein. Synthetic peptides of the N-terminus of PrP killed the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, and the Gram-positive Bacillus subtilis and Staphylococcus aureus, as well as the fungus Candida parapsilosis. Fluorescence studies of peptide-treated bacteria, paired with analysis of peptide effects on liposomes, showed that the peptides exerted membrane-breaking effects similar to those seen after treatment with the "classical" human antimicrobial peptide LL-37. In contrast to LL-37, however, no marked helix induction was detected for the PrP-derived peptides in presence of negatively charged (bacteria-mimicking) liposomes. PrP furthermore showed an inducible expression during wounding of human skin ex vivo and in vivo, as well as stimulation of keratinocytes with TGF-alpha in vitro. CONCLUSIONS: The demonstration of an antimicrobial activity of PrP, localisation of its activity to the N-terminal and heparin-binding region, combined with results showing an increased expression of PrP during wounding, indicate that PrPs could have a previously undisclosed role in host defense

Clinical, immunological and bacteriological evaluation of adverse reactions to skin-penetrating titanium implants in the head and neck region

Between 1977 and October 1989, 445 patients have been treated with bone-anchored skin-penetrating titanium implants for anchorage of facial prostheses or bone-conducting hearing aids, at the Ear, Nose and Throat Department at Sahlgren's Hospital in Gothenburg. The majority of patients had no adverse skin reactions, while a few patients were responsible for the majority of the adverse reactions. The aim of our study was to analyse differences between these groups. We started a clinical study on 9 patients with a clinical history of adverse skin reactions around the titanium implants and 9 patients without adverse skin reactions were used as controls. None of the patients had delayed hypersensitivity to titanium. Microbiological analyses showed that when there was clinical irritation, Staphylococcus aureus could be isolated