Wound Healing Activity and Mechanisms of Action of an Antibacterial Protein from the Venom of the Eastern Diamondback Rattlesnake (Crotalus adamanteus)

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.

Symbiosis theory-directed green synthesis of silver nanoparticles and their application in infected wound healing

“…roles in wound healing. 37 Herein, the levels of TNF-α, IL-1β, and IL-6 in wound tissue homogenates were measured 21 days after treatment. Wounds treated with either AgNPs or povidone-iodine had significantly lower levels of TNF-α and IL-6 throughout the healing process (P,0.05) than those of the control group ( Figure 5).…”

Novel phospholipase A2 inhibitors from python serum are potent peptide antibiotics

“…Infected control mice were treated with either 0.2% Fusidic Acid Ointment (FAO), which served as a drug control, or sterile water (wound control or Wctrl). Treatment was subsequently applied daily from 0 to 4 days, and the reduction of the wound measurement was accomplished by using tracing paper once every 2 days up to 14 days [39].…”

“…Proteins and peptides modulate NF-kB activation during wound repair in mice [78]. Following peptide treatment, e-cadherin, TGFR1, fibronectin and VEGF contents were found to be highly expressed at the wound sites as measured by western blot analysis compared to wound controls in which the contents were expressed only faintly.…”

Vipericidins, Snake Venom Cathelicidin-Related Peptides, in the Milieu of Reptilian Antimicrobial Polypeptides

“…Snake venom PLA 2 exhibits antibacterial (Perumal Samy et al 2007;Samy et al 2012) and antiviral activity (Muller et al 2014). For example, the basic svPLA2 from the venom of the eastern diamondback rattlesnake (Crotalus adamanteus) -CaTx-II -is a potent non-cytotoxic bactericide that kills pathogenic Staphylococcus aureus, Burkholderia pseudomallei, and Enterobacter aerogenes by inducing pore formation and membrane disruption (Samy et al 2014). Compared to CaTx-II, the antimicrobial activity exclusively against Gram-negative bacteria resides in the b-chain of the heterodimeric neurotoxic svPLA2 (b-bungarotoxin) from the Taiwan banded krait Bungarus multicinctus (Wen et al 2013).…”