A plausible mode of action of pseudin-2, an antimicrobial peptide from Pseudis paradoxa

►We found that pseudin-2 organized to an aggregated state in aqueous solution, but that it dissociated into monomers upon binding to lipopolysaccharide (LPS), even though it did not neutralize LPS in Gram-negative bacteria. ►pseudin-2 assumed an α-helical structure in the presence of biological membranes and formed pores in both bacterial and fungal membranes, through which it entered the cytoplasm and tightly bound to RNA. ►The potent antimicrobial activity of pseudin-2 likely results from both the formation of pores capable of collapsing the membrane potential and releasing intracellular materials and its inhibition of macromolecule synthesis through its binding to RNA.