Characterization of BmKbpp, a multifunctional peptide from the Chinese scorpion Mesobuthus martensii Karsch: gaining insight into a new mechanism for the functional diversification of scorpion venom peptides.

BmKbpp is a novel cationic and α-helical peptide from the Chinese scorpion Mesobuthus martensii Karsch, of which function or biological activity has not been characterized so far. Here we showed that BmKbpp possesses strong antimicrobial activity against both Gram-positive and Gram-negative bacteria with a MIC range from 2.3 μM to 68.2 μM for the majority of tested bacteria. BmKbpp also inhibits the growth of tested fungi with an IC50 range from 0.2 μM to 3.1 μM. Because BmKbpp potently inhibits the growth of some antibiotics-resistant pathogens, and shows very weak hemolytic activity, it has considerable potentials for therapeutic applications. Moreover, we found that BmKbpp markedly inhibits the superoxide production in granulocytes or HL-60 cells at the concentrations of submicromolar level; this suggests that BmKbpp can act as a signaling molecule involving innate immune regulation at low concentrations. The C-terminal region of BmKbpp (BmKbpp-C) shows 72% similarity to the peptide K-12, a bradykinin-potentiating peptide. We found that both BmKbpp and BmKbpp-C possess bradykinin-potentiating activity, and the activity of BmKbpp-C is stronger than that of BmKbpp. PCR amplification for the genomic gene of BmBpp showed that it is not a continuous sequence in the genome; it suggests that BmKbpp could come from a recombination event in transcript level. Taken together, our data suggest that multi-functionalization of a single peptide, which is probably mediated by trans-splicing, could be a new mechanism for the functional diversification of scorpion venom peptides.