Abstract
Basic phospholipase A2 was identified from the venom of the eastern diamondback rattlesnake. The Crotalus adamanteus toxin-II (CaTx-II) induced bactericidal effects (7.8 µg/ml) on Staphylococcus aureus, while on Burkholderia pseudomallei (KHW), and Enterobacter aerogenes were killed at 15.6 µg/ml. CaTx-II caused pore formation and membrane damaging effects on the bacterial cell wall. CaTx-II was not cytotoxic on lung (MRC-5), skin fibroblast (HEPK) cells and in mice. CaTx-II-treated mice showed significant wound closure and complete healing by 16 days as compared to untreated controls (**P<0.01). Histological examination revealed enhanced collagen synthesis and neovascularization after treatment with CaTx-II versus 2% Fusidic Acid ointment (FAO) treated controls. Measurement of tissue cytokines revealed that interleukin-1 beta (IL-1β) expression in CaTx-II treated mice was significantly suppressed versus untreated controls. In contrast, cytokines involved in wound healing and cell migration i.e., monocyte chemotactic protein-1 (MCP-1), fibroblast growth factor-basic (FGF-b), chemokine (KC), granulocyte-macrophage colony-stimulating factor (GM-CSF) were significantly enhanced in CaTx-II treated mice, but not in the controls. CaTx-II also modulated nuclear factor-kappa B (NF-κB) activation during skin wound healing. The CaTx-II protein highlights distinct snake proteins as a potential source of novel antimicrobial agents with significant therapeutic application for bacterial skin infections.
Highlights
Antimicrobial proteins and peptides play a major role in innate immunity by interacting directly with bacteria and killing them [1]
Crotalus adamanteus toxin-II (CaTx-II) possessed the highest activity of any Phospholipase A2 (PLA2) purified from C. adamanteus venom
We found that the treatment with CaTx-II substantially inhibited constitutive p65 phosphorylation that was observed in wound control mice (Fig. 4 H)
Summary
Antimicrobial proteins and peptides play a major role in innate immunity by interacting directly with bacteria and killing them [1]. These multifunctional proteins have wound healing activity and receptor-mediated effects on eukaryotic cells [2]. Antibiotics used for treatment of Staphylococcus aureus infected surgical wounds and other skin related infections include methicillin [9], vancomycin [10], glycopeptides [11], and betalactams [12]. Following S. aureus infection, wound healing after treatment with some of these antibiotics has been reported to be only moderately successful in many cases [13]
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