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. 2008 Jun;52(6):2205-11.
doi: 10.1128/AAC.01340-07. Epub 2008 Apr 7.

RNAIII-inhibiting peptide enhances healing of wounds infected with methicillin-resistant Staphylococcus aureus

Oriana Simonetti  1 , Oscar Cirioni, Roberto Ghiselli, Gaia Goteri, Alessandro Scalise, Fiorenza Orlando, Carmela Silvestri, Alessandra Riva, Vittorio Saba, Kiran D Madanahally, Annamaria Offidani, Naomi Balaban, Giorgio Scalise, Andrea Giacometti
Affiliations

RNAIII-inhibiting peptide enhances healing of wounds infected with methicillin-resistant Staphylococcus aureus

Oriana Simonetti et al. Antimicrob Agents Chemother. 2008 Jun.

Abstract

Quorum sensing is a mechanism through which a bacterial population receives input from neighboring cells and elicits an appropriate response to enable survival within the host. Inhibiting quorum sensing by RNAIII-inhibiting peptide (RIP) has been demonstrated as a very effective mode of prevention and therapy for device-associated staphylococcal infections and was tested here for healing of wounds that are otherwise resistant to conventional antibiotics. Wounds, established through the panniculus carnosus of BALB/c mice, were inoculated with 5 x 10(7) CFU of methicillin-resistant Staphylococcus aureus. Mice were treated with Allevyn, RIP-soaked Allevyn (containing 20 microg RIP), daily intraperitoneal teicoplanin (7 mg/kg of body weight), Allevyn and teicoplanin, and RIP-soaked Allevyn and daily intraperitoneal teicoplanin. The main outcome measures were quantitative bacterial culture and histological examination with assessment of microvessel density and of vascular endothelial growth factor (VEGF) expression in tissue sections. Treatment with RIP-soaked Allevyn together with teicoplanin injection greatly reduced the bacterial load to 13 CFU/g (control untreated animals had 10(8) CFU/g bacteria). All other treatments were also significantly effective but only reduced the bacterial load to about 10(3) CFU/ml. Histological examination indicated that only treatment with RIP-soaked Allevyn with teicoplanin injection restored epithelial, granulation, and collagen scores, as well as microvessel density and VEGF expression, to the levels found with uninfected mice. In conclusion, we observed that RIP may be useful for the management of infected wounds and that it could represent an exciting and future alternative to the conventional antibiotics, at present considered the gold-standard treatments for methicillin-resistant S. aureus infections.

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Figures

FIG. 1.
FIG. 1.
Bacterial loads in wounds of untreated and treated animals.
FIG. 2.
FIG. 2.
Histological features of wounds of untreated and treated animals. (A) A wound from a noninfected mouse is shown with a complete and normal epidermis (reepithelization score of 4), a collagenized granulation tissue with few fibroblasts (granulation tissue formation score of 4), and a marked collagen organization (score of 4). (B) A wound from a MRSA-infected mouse without treatment shows an incomplete epidermis (reepithelization score of 1), a hypocellular granulation tissue with few vessels (granulation tissue formation score of 1), and traces of collagen organization (score of 1). Treatment with drug-free Allevyn (C), drug-free Allevyn and daily parenteral or intraperitoneal teicoplanin (D), and daily parenteral or intraperitoneal teicoplanin alone (E) resulted in a higher degree of wound repair with a hypertrophic epidermis (reepithelization score of 3) in all cases, granulation tissue with many vessels and some fibroblasts and inflammatory cells (granulation tissue formation score of 2), and moderate collagen organization (score of 3). (F) A wound treated with RIP-soaked Allevyn bears many similarities with the case depicted in panel A, with a complete and normal epidermis (reepithelization score of 4), a collagenized granulation tissue with few fibroblasts (granulation tissue formation score of 4), and a marked collagen organization (score of 4). Panels G to J show immunostaining for VEGF in wounds of untreated and treated animals. (G) A wound from a noninfected mouse shows strong immunostaining in epidermal and adnexal epithelial cells as well as in fibroblasts and vessels of the dermis. (H) A wound from a MRSA-infected mouse without treatment shows faint to moderate staining only in the epidermis and not in the dermal fibroblastic, inflammatory, and endothelial cells. Treatment with drug-free Allevyn (I) resulted in a higher degree of VEGF expression in the epidermis and in a moderate number of vessels, fibroblasts, and inflammatory cells. (J) A wound treated with RIP-soaked Allevyn bears many similarities with the case depicted in panel G, with strong immunostaining in epidermal epithelial cells as well as in fibroblasts and vessels of the dermis.
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