Antimicrobial Proteins from Snake Venoms: Direct Bacterial Damage and Activation of Innate Immunity Against Staphylococcus aureus Skin Infection

Abstract

The innate immune system is the first line of defense against microbial diseases. Antimicrobial proteins produced by snake venoms have recently attracted significant attention due to their relevance to bacterial infection and potential development into new therapeutic agents. Staphylococcus aureus is one of the major human pathogens causing a variety of infections involving pneumonia, toxic shock syndrome, and skin lesions. With the recent emergence of methicillin (MRSA) and vancomycin (VRSA) resistance, S. aureus infection is a serious clinical problem that will have a grave socio-economic impact in the near future. Although S. aureus susceptibility to innate antimicrobial peptides has been reported recently, the protective effect of snake venom phospholipase A₂ (svPLA₂) proteins on the skin from S. aureus infection has been understudied. This review details the protective function of svPLA₂s derived from venoms against skin infections caused by S. aureus. We have demonstrated in vivo that local application of svPLA₂ provides complete clearance of S. aureus within 2 weeks after treatment compared to fusidic acid ointment (FAO). In vitro experiments also demonstrate that svPLA₂ proteins have inhibitory (bacteriostatic) and killing (bactericidal) effects on S. aureus in a dose-dependant manner. The mechanism of bacterial membrane damage and perturbation was clearly evidenced by electron microscopic studies. In summary, svPLA₂s from Viperidae and Elapidae snakes are novel molecules that can activate important mechanisms of innate immunity in animals to endow them with protection against skin infection caused by S. aureus.

Interactions of PLA2-s from Vipera lebetina, Vipera berus berus and Naja naja oxiana Venom with Platelets, Bacterial and Cancer Cells

“…For example, sPLA 2 s have been shown to be inhibitory (bacteriostatic) or killing (bactericidal) to gram-positive bacteria Staphylococcus aureus [37]. In case of svPLA 2 from Crotalus durissus collilineatus venom the bactericidal effect was entirely dependent on its enzymatic activity [38].…”

Staphylococcal Superantigens Spark Host-Mediated Danger Signals

“…For various reasons, alternative methods for treating ­antibiotic-resistant strains of S. aureus (i.e., MRSA) are being explored by different groups around the world ( 16 – 23 ). Some of the exotic sources for these novel drugs include snake venom, tree bark/stems/leaves, and carnivorous plants.…”

Peptidomic Analysis of Animal Venoms

“…Therefore, the components of animal venoms are important biological tools for studying these receptors, and the discovery of molecules in venoms with selective activity for these receptors represents a very attractive approach to the search for new drugs. The venom components may therefore be probed for the development of new therapies for pain management [31], new anti-arrhythmic [32], anticonvulsant [33] or anxiolytic drugs [34], new antimicrobial agents [35][36][37] or pesticides [38,39], etc. Even a substance that causes priapism has been isolated from the venom of a Brazilian spider [40], becoming a potential drug candidate to attend erectile dysfunction.…”