Journal
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
Volume 32, Issue 5, Pages 392-397Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijantimicag.2008.05.005
Keywords
Defensin; MRSA; Antimicrobial peptides
Funding
- Enterprise Ireland Commercialisation Fund [PC/2005/0242]
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beta-Defensin antimicrobial peptides are critical components of the innate immune response in many species and may be useful against pathogens that have acquired resistance to standard antibiotic therapies. We analysed a panel of recently discovered bovine beta-defensins in order to identify sites that may have particular functional importance against antibiotic-resistant bacteria. Modifications were introduced to increase charge at positively selected( PS) sites, to make charge-neutral changes at PS sites, to increase hydrophobicity and to confer a hydrophilic C-terminal. Whilst all four peptide modi. cations increased antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) compared with the native form of bovine beta-defensin 123 (P=0.02), conferring the hydrophilic tail caused the most significant increase, with a 50% lethal dose (LD50) of 3.91 mu g/mL. The peptide with increased charge at PS sites showed the most significant increase in antimicrobial activity against a non-resistant strain of S. aureus (P=0.02). Therefore, informed modi. cations of the amino acid sequence can significantly affect the specificity and antimicrobial activity of a peptide. (C) 2008 Elsevier B. V. and the International Society of Chemotherapy. All rights reserved.
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