Activity of a killer peptide on the growth and ultrastructure of leishmaniae

An engineered killer decapeptide (KP) has been recently synthesized based on the sequence of a recombinant, single-chain anti-idiotypic antibody acting as a functional internal image of a yeast killer toxin. This KP exerts a microbicidal activity by an interaction with β-glucan present in the surface of many microorganisms, in particular fungi. The activity of KP against the “in vitro” growth and vitality of promastigotes of two Leishmania species has been evaluated and compared with the activity due to a “scramble” irrelevant decapeptide (SP). The IC50 of KP corresponds to 7.2 × 10−5mol/litre for Leishmania infantum, whereas both the inhibitory and leishmanicidal activity is superior on Leishmania major. Moreover, an increase of activity was observed by treating protozoa again with KP; SP is inactive. Structural damages of promastigotes were revealed by transmission electron microscopic studies; the treatment with KP induces a cell death via a non-apoptotic process. In particular, intracellular damage including cytoplasmic degeneration without disruption of the plasma membrane was noted. The activity of KP on leishmania promastigotes seems governed by ionic and/or electrostatic interactions with the glycoconjugates present on the surface of the parasite inducing an authophagic cell degeneration.