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 (PLA2s) 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 PLA2s 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 PLA2s to efficient drugs will be equally addressed.

Evaluation of the Effectiveness of Crotoxin as an Antiseptic against Candida spp. Biofilms

“…Other bacterial membrane structures, such as glucans and ergosterol, have been identified as important targets for antimicrobials as well [23]. Moreover, the amino acid cysteine has been shown to partially inhibit C. albicans germination, suggesting that the presence of cysteine residues in both crotapotin and PLA 2 subunits of CTX would disrupt cell surface hydrophobicity with consequent cell death [18,24]. In this paper, we have demonstrated that Candida spp.…”

“…Nonetheless, the in vitro antimicrobial and antibiofilm activity of native CTX was superior to that of the conventional nystatin. This suggests a specific mechanism of action that may be related to the membrane damaging activities of the PLA 2 subunit of CTX [18]. In addition, the differences in the glycerophospholipid compositions found in different Candida species could account for the variations in CTX antimicrobial activity against the two strains investigated herein [20][21][22].…”

“…Cationic antimicrobial proteins, such as svPLA 2 , act by a process of thinning and destabilization of the membrane lipid bilayer, resulting in the permeabilization and expulsion of cellular content. It has been suggested that cationic and hydrophobic regions of svPLA 2 are responsible for the molecular permeation, due to their high affinity for phospholipid head groups [18]. Furthermore, apart from protein-mediated lysis, it has been proposed that PLA 2 s also inhibit the biosynthesis of macromolecules and promote the expression of autolytic enzymes [18].…”

“…It has been suggested that cationic and hydrophobic regions of svPLA 2 are responsible for the molecular permeation, due to their high affinity for phospholipid head groups [18]. Furthermore, apart from protein-mediated lysis, it has been proposed that PLA 2 s also inhibit the biosynthesis of macromolecules and promote the expression of autolytic enzymes [18]. Other bacterial membrane structures, such as glucans and ergosterol, have been identified as important targets for antimicrobials as well [23].…”

Pan-Drug Resistant Acinetobacter baumannii, but Not Other Strains, Are Resistant to the Bee Venom Peptide Melittin

“…Several strategies have been proposed over the years in an attempt to efficiently treat bacterial biofilms, including prevention, weakening, disruption or killing [49]. Among the limited numbers of new antimicrobials in the pipeline, natural peptides from animal venoms have been demonstrated to possess promising biological properties, which warrant their development as efficacious agents against recalcitrant pathogens [50][51][52]. Among them, melittin from bee venom has been proven to have potent antibacterial activity [31].…”