Wound healing activity and mechanisms of action of an antibacterial protein from the venom of the eastern diamondback rattlesnake (Crotalus adamanteus)

Ramar Perumal Samy, Matheswaran Kandasamy, Ponnampalam Gopalakrishnakone, Bradley G. Stiles, Edward G. Rowan, David Becker, Muthu K. Shanmugam, Gautam Sethi, Vincent T K Chow

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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. 

Original languageEnglish
Article numbere80199
Number of pages16
JournalPLOS One
Volume9
Issue number2
DOIs
Publication statusPublished - 14 Feb 2014

Keywords

  • Crotalus adamanteus toxin-II
  • CaTx-II
  • antimicrobial agents
  • bacterial skin infections
  • snake proteins

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    Samy, R. P., Kandasamy, M., Gopalakrishnakone, P., Stiles, B. G., Rowan, E. G., Becker, D., Shanmugam, M. K., Sethi, G., & Chow, V. T. K. (2014). Wound healing activity and mechanisms of action of an antibacterial protein from the venom of the eastern diamondback rattlesnake (Crotalus adamanteus). PLOS One, 9(2), [e80199]. https://doi.org/10.1371/journal.pone.0080199