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

Drug Dev Res. 2019 Feb;80(1):68-85. doi: 10.1002/ddr.21456. Epub 2018 Sep 26.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antimicrobial Cationic Peptides / isolation & purification
  • Antimicrobial Cationic Peptides / pharmacology
  • Drug Resistance, Microbial / drug effects*
  • Drug Resistance, Microbial / physiology
  • Humans
  • Phospholipases A2 / isolation & purification*
  • Phospholipases A2 / pharmacology*
  • Snake Venoms / enzymology*
  • Snake Venoms / pharmacology*

Substances

  • Antimicrobial Cationic Peptides
  • Snake Venoms
  • Phospholipases A2