Harnessing snake venom phospholipases A2 to novel approaches for overcoming antibiotic resistance

Abstract

The emergence of antibiotic resistance drives an essential race against time to reveal new molecular structures capable of addressing this alarming global health problem. Snake venoms are natural catalogs of multifunctional toxins and privileged frameworks, which serve as potential templates for the inspiration of novel treatment strategies for combating antibiotic resistant bacteria. Phospholipases A₂ (PLA₂ s) are one of the main classes of antibacterial biomolecules, with recognized therapeutic value, found in these valuable secretions. Recently, a number of biomimetic oligopeptides based on small fragments of primary structure from PLA₂ toxins has emerged as a meaningful opportunity to overcome multidrug-resistant clinical isolates. Thus, this review will highlight the biochemical and structural properties of antibacterial PLA₂ s and peptides thereof, as well as their possible molecular mechanisms of action and key roles in development of effective therapeutic strategies. Chemical strategies possibly useful to convert antibacterial peptides from PLA₂ s to efficient drugs will be equally addressed.

Keywords: antibacterial peptides; antibiotic-resistant bacteria; peptidomimetics; phospholipase A2; snake venom.