Structural and functional characterisation of isolated puff adder (Bitis arietans) venom serine proteases

Posted by
  Structural and functional characterisation of isolated puff adder (Bitis arietans) venom serine proteases Abstract Serine proteases (SVSPs) are known to play a major role in the haemotoxic actions of viper venom, but compared with those from other medically important vipers, the serine proteases of puff adder venoms have not been extensively characterised. To address this, we isolated, identified and characterised the bioactivity of the serine proteases within the venom of the Nigerian puff adder, which we had previously shown to be especially rich in this class of toxin. Two distinct groups were identified, each with different protein substrate specificities. Both had similar molecular weights of 52-62 kDa, with 4-6 N-glycans, but one group consisted of trypsin-like acidic SVSPs and the other of non-trypsin-like basic SVSPs with a specificity for aliphatic amino acids at the P 1 position. Each acted differently on fibrinogen: the acidic SVSPs showed thrombin-like alpha/beta-fib...

Scorpion venom-derived Opis16a shows potent membrane-destabilising Gram-negative activity and promising in vivo topical efficacy

Posted by

 


Scorpion venom-derived Opis16a shows potent membrane-destabilising Gram-negative activity and promising in vivo topical efficacy

Abstract

Antimicrobial peptides (AMPs) are lead candidates for antibacterial drug development, especially against multidrug-resistant Gram-negative bacteria. Previously, we showed that Opis16a, a novel scorpion venom-derived AMP, exhibits broad-spectrum activity against drug-resistant Gram-negative strains with minimal toxicity to mammalian cells. However, its mechanism of action remained unclear. Here, we show that Opis16a rapidly kills Gram-negative bacteria by targeting and disrupting their membranes, with strong bacterial selectivity over HaCaT and HepG2 cell lines. Mechanistic studies in Escherichia coli and a clinically relevant multidrug-resistant Acinetobacter baumannii strain reveal that Opis16a interacts with lipopolysaccharides, destabilising the outer membrane and causing inner membrane depolarisation and permeabilisation within minutes. Opis16a’s strong activity (MIC: 8 µg/mL), selectivity, and membrane disruption, along with its serum stability, translates into successful therapy in an in vivo Galleria mellonella model of gentamicin-resistant A. baumannii wound infection. Opis16a emerges as a novel membrane-destabilising AMP with promising potential for topical use against resistant Gram-negative infections.

Oosthuizen, C. B., Mason, A. J., Bester, M. J., & Gaspar, A. R. (2026). Scorpion venom-derived Opis16a shows potent membrane-destabilising Gram-negative activity and promising in vivo topical efficacy. Npj Antimicrobials and Resistance. https://doi.org/10.1038/s44259-026-00266-9