Please use this identifier to cite or link to this item: http://hdl.handle.net/1893/8712
Appears in Collections:Aquaculture Journal Articles
Peer Review Status: Refereed
Title: In vivo efficacy of the antimicrobial peptide ranalexin in combination with the endopeptidase lysostaphin against wound and systemic meticillin-resistant Staphylococcus aureus (MRSA) infections
Author(s): Desbois, Andrew P
Gemmell, Curtis G
Coote, Peter J
Contact Email: andrew.desbois@stir.ac.uk
Keywords: Antibacterial
Antibiotic resistance
Bactericidal
Kidney burden
Staphylococcus aureus
Synergy
Issue Date: Jun-2010
Date Deposited: 31-Aug-2012
Citation: Desbois AP, Gemmell CG & Coote PJ (2010) In vivo efficacy of the antimicrobial peptide ranalexin in combination with the endopeptidase lysostaphin against wound and systemic meticillin-resistant Staphylococcus aureus (MRSA) infections. International Journal of Antimicrobial Agents, 35 (6), pp. 559-565. http://www.scopus.com/inward/record.url?partnerID=yv4JPVwI&eid=2-s2.0-77951767027&md5=b041aa27abe16309e9406aa5efcb7c84; https://doi.org/10.1016/j.ijantimicag.2010.01.016
Abstract: New treatments are urgently required for infections caused by meticillin-resistant Staphylococcus aureus (MRSA) as these strains are often resistant to multiple conventional antibiotics. Earlier studies showed that ranalexin, an antimicrobial peptide (AMP), in combination with lysostaphin, an antistaphylococcal endopeptidase, synergistically inhibits the growth of MRSA, meaning that it deserved consideration as a new anti-S. aureus therapy. Using haemolysis and Vero cell viability assays, ranalexin with lysostaphin is proven to be non-toxic at antibacterial concentrations. In human serum, ranalexin with lysostaphin is significantly more effective against MRSA than treatment with either component alone. In a rabbit model of wound infection, ranalexin with lysostaphin reduced MRSA in the wound by ca. 3.5 log10 colony-forming units (CFU) compared with the untreated control. The combination is significantly more effective than treatment with ranalexin or lysostaphin alone. In a mouse model of systemic infection, ranalexin with lysostaphin reduced MRSA kidney burden by ca. 1 log10 CFU/g compared with untreated controls or treatment with ranalexin or lysostaphin alone. Importantly, the combination is synergistically bactericidal against various S. aureus isolates in vitro, including those with reduced susceptibility to lysostaphin or vancomycin. Ranalexin and lysostaphin could be incorporated in wound dressings for the prevention and treatment of topical S. aureus infections. That AMPs can enhance the antibacterial effectiveness of lysostaphin in vivo highlights a new avenue of research in the fight against drug-resistant staphylococci.
URL: http://www.scopus.com/inward/record.url?partnerID=yv4JPVwI&eid=2-s2.0-77951767027&md5=b041aa27abe16309e9406aa5efcb7c84
DOI Link: 10.1016/j.ijantimicag.2010.01.016
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