JAC Advance Access originally published online on February 8, 2007
Journal of Antimicrobial Chemotherapy 2007 59(3):493-498; doi:10.1093/jac/dkl513
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Antimicrobial activity of the recombinant designer host defence peptide P-novispirin G10 in infected full-thickness wounds of porcine skin
1 Department of Plastic Surgery, Burn Centre, BG University Hospital Bergmannsheil, Ruhr University Bochum, Buerkle-de-la Camp Platz 1, 44789 Bochum, Germany 2 Novozymes A/S, Bagsvaerd, Denmark 3 Department for Microbiology, Ruhr University Bochum, Bochum, Germany
Received 21 April 2006; returned 17 July 2006; revised 23 October 2006; accepted 8 November 2006
* Corresponding author. Tel: +49-234-302-3442; Fax: +49-234-302-6379; E-mail: lars.steinstraesser{at}ruhr-uni-bochum.de
Objectives: The growing number of patients with impaired wound healing and the development of multidrug-resistant bacteria demand the investigation of alternatives in wound care. The antimicrobial activity of naturally occurring host defence peptides and their derivatives could be one alternative to the existing therapy options for topical treatment of wound infection. Therefore, the aim of this study was to investigate the antimicrobial activity of proline-novispirin G10 (P-novispirin G10) in vitro and in the infected porcine titanium wound chamber model.
Methods: The new derived designer host defence peptide P-novispirin G10 was tested in vitro against Gram-positive and Gram-negative bacterial strains. Additionally, cytotoxicity and haemolytic activities of P-novispirin G10 and protegrin-1 were measured. For in vivo studies, six wound chambers were implanted on each flank of Göttinger minipigs (n = 2, female, 6 months old, 15–20 kg). Eleven wound chambers were inoculated 8 days post-operatively with 5 x 108 of Staphylococcus aureus; one wound chamber remained uninfected as a system control. After wound infection had been established (4 days after inoculation), each wound chamber was topically treated with P-novispirin G10, protegrin-1 or carrier control. Wound fluid was harvested every hour for a total follow up of 3 h.
Results: P-novispirin G10 demonstrated broad-spectrum antimicrobial activity with moderate haemolytic and cytotoxic activities compared with protegrin-1. In the infected wound chamber model P-novispirin G10 demonstrated a 4 log10 reduction in bacterial counts.
Conclusions: This implicates the potential of P-novispirin G10 as an alternative in future antimicrobial wound care. However, more studies are necessary to further define clinical applications and potential side effects in greater detail.
Keywords: antimicrobial peptides , innate immunity , wound infection , animal model