Novel cytotoxity exhibition mode of polybia-CP, a novel antimicrobial peptide from the venom of the social wasp Polybia paulista

Antimicrobial peptide polybia-CP was purified from the venom of the social wasp Polybia paulista. It has an amphipathic sequence ILGTILGLLKSL-NH2 and possesses potent antimicrobial activity against both Gram-positive and Gram-negative bacteria. In this study we synthesized polybia-CP, studied its cytotoxity on tumor cells and proposed its possible mechanism. Our results revealed that polybia-CP exerts its cytotoxic efficacy by disrupting the integrity of cell membrane. Furthermore, molecular dynamics (MD) simulations were employed to investigate the mechanism of membrane perturbation. Both the MD simulations and the experimental data indicated that polybia-CP takes a standard α-helix conformation in the membrane. These findings together with the other experimental results support a speculation of mechanism similar to the “carpet” model.

► We first report the novel cytotoxity exhibition mode of polybia-CP ► We first use MD simulations method to clarify the action mechanism of polybia-CP ► Polybia-CP was not affected by the conventional multi-drug resistant mechanism ► Polybia-CP may represent a novel therapeutic strategy in the treatment of tumor and microbe infection, especially the increasing multidrug resistance problem.