Screening the antimicrobial properties of snake venoms: an iterative fractionation approach

Antimicrobial resistance increasingly poses a significant global health challenge. New antimicrobials are desperately needed, driving the need to explore novel sources of natural products. Snake venom has shown promise due to the complex mixture of proteins and peptides which demonstrate therapeutic utility in other aspects of healthcare. In this study, we took an iterative approach to screen 14 snake venoms against Escherichia coli and Klebsiella pneumoniae and identify venom-derived proteins with diverse activity against E. coli. Six venoms exhibited significant near-complete inhibitory activity, and four were retained after dialysis, confirming that the inhibitory effect was due to high-molecular-weight components above 3.5 kDa. Fractionation of two active venoms from Naja mossambica and Naja subfulva revealed protein fractions which have either subtle or significant antimicrobial activity. SDS-PAGE and mass spectrometry identified phospholipase A₂ isoforms in N. mossambica venom fractions and neurotoxic proteins (long and short neurotoxins) in N. subfulva venom fractions as potential antimicrobials.