Viper metalloproteinase (Agkistrodon halys pallas) with antimicrobial activity against multi-drug resistant human pathogens.
Metalloproteinases are abundant enzymes in crotalidae and viperidae snake venoms. Snake venom metalloproteinases (SVMPs) comprise a family of zinc-dependent enzymes, which display many different biological activities. A 23.1 kDa protein was isolated from Agkistrodon halys (pallas, Chinese viper) snake venom. The toxin is a single chain polypeptide with a molecular weight of 23146.61 and an N-terminal sequence (MIQVLLVTICLAVFPYQGSSIILES) relatively similar to that of other metalloprotein-like proteases isolated from the snake venoms of the Viperidae family. The antibacterial effect of Agkistrodon halys metalloproteinase (AHM) on Burkholderia pseudomallei (strains TES and KHW), Escherichia coli, Enterobacter aerogenes, Proteus vulgaris, Proteus mirabilis, Pseudomonas aeruginosa (Gram-negative bacteria) and Staphylococcus aureus (Gram-positive bacterium) was studied at a concentration 120 microM. Interestingly, we found that the metalloproteinase exhibited antibacterial properties and was more active against S. aureus, P. vulgaris, P. mirabilis and multi-drug resistant B. pseudomallei (strain KHW) bacteria. AHM variants with high bacteriostatic activity (MIC 1.875-60 microM) also tended to be less cytotoxic against U-937 human monocytic cells up to 1 mM concentrations. These results suggest that this metalloprotein exerts its antimicrobial effect by altering membrane packing and inhibiting mechanosensitive targets.
Samy
Ramar Perumal
RP
Venom and Toxin Research Programme, Yong Loo Lin School of Medicine, Department of Anatomy, National University of Singapore, Singapore, Singapore.
Gopalakrishnakone
Ponnampalam
P
Chow
Vincent T K
VT
Ho
Bow
B
D017836:Agkistrodon / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000378:metabolism* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects / Q000648:ultrastructure; D002460:Cell Line; D003435:Crotalid Venoms / Q000201:enzymology* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D024901:Drug Resistance, Multiple, Bacterial; D006801:Humans; D045726:Metalloproteases / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D016415:Sequence Alignment
D000890:Anti-Infective Agents; D003435:Crotalid Venoms; D045726:Metalloproteases