Surgical implants coated with one of 'nature's antibiotics' could prevent infection
1st on the web (February 3, 2009)
February 2009
Researchers at the University of British Columbia have discovered a mimic of one of "nature's antibiotics" that can be used to coat medical devices to prevent infection and rejection.
The study, published in the Jan. 30 issue of
Chemistry & Biology, found that a synthetic form – short tethered cationic antimicrobial peptides (cationic peptide) – can protect surfaces, killing bacteria and fungi that come into contact with them. The discovery could lead to new protection for surgical implants, catheters, hip replacements and joint prostheses.
“The rapid progress of biomedical technology and an aging population places increasing demands on medical implants to treat serious tissue disorders and replace organ function,” Robert Hancock, principal investigator and Canada Research Chair in Pathogenomics and Antimicrobials at UBC’s Department of Microbiology and Immunology, said in a press release. “These cationic peptides are currently being developed as soluble antibiotics for administration to patients to combat infection. We have developed a new method for finding a variety of effective peptides that can bind to a surface and still kill harmful bacteria and fungus.”
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Chemistry & Biology
Volume 16, Issue 1, 30 January 2009, Pages 58-69
Screening and Characterization of Surface-Tethered Cationic Peptides for Antimicrobial Activity
Kai Hilpert1, 6, Melissa Elliott1, Håvard Jenssen1, Jason Kindrachuk1, Christopher D. Fjell1, Jana Körner2, Dirk F.H. Winkler3, Lindsay L. Weaver4, Peter Henklein5, Anne S. Ulrich6, Sandy H.Y. Chiang1, Susan W. Farmer1, Nelly Pante4, Rudolf Volkmer2 and Robert E.W. Hancock1, ,
1. Centre for Microbial Diseases and Immunity Research, University of British Columbia, 2259 Lower Mall Research Station, Vancouver, BC V6T 1Z3, Canada
2. Institut für Medizinische Immunologie, Universitätsklinikum Charité, Humboldt-Universität zu Berlin, Hessische Str. 3-4, 10117 Berlin, Germany
3. Peptide Array Facility of the Brain Research Centre, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC V6T 2B5, Canada
4. Department of Zoology, University of British Columbia, 6270 University Boulevard, Vancouver, BC V6T 1Z4, Canada
5. Institut für Biochemie, Universitätsklinikum Charité, Humboldt-Universität zu Berlin, Monbijoustrasse 2, 10117 Berlin, Germany
6. Karlsruhe Institute of Technology, Institute of Biological Interfaces, POB 3640, 76021 Karlsruhe, Germany
Summary
There is an urgent need to coat the surfaces of medical devices, including implants, with antimicrobial agents to reduce the risk of infection. A peptide array technology was modified to permit the screening of short peptides for antimicrobial activity while tethered to a surface. Cellulose-amino-hydroxypropyl ether (CAPE) linker chemistry was used to synthesize, on a cellulose support, peptides that remained covalently bound during biological assays. Among 122 tested sequences, the best surface-tethered 9-, 12-, and 13-mer peptides were found to be highly antimicrobial against bacteria and fungi, as confirmed using alternative surface materials and coupling strategies as well as coupling through the C and N termini of the peptides. Structure-activity modeling of the structural features determining the activity of tethered peptides indicated that the extent and positioning of positive charges and hydrophobic residues were influential in determining activity.
Author Keywords: CHEMBIO; MICROBIO
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