D-Cateslytin peptide

The peptide cateslytin (RSMRLSFRARGYGFR) produced by enzymatic degradationof stress proteins is remarkably active against a large number of microorganisms including Plasmodium Falciparum responsible for Malaria. Its mode of action on membranes mimicking the external negatively charged membrane of these microorganisms has been studied by circular dichroism, infra-red (attenuatedtotal reflection), high-resolution magic angle sample spinning and wide line solid state NMR, patch clamp and molecular dynamics. The peptide, which is unstructuredin solution, adopts an aggregated beta sheet structure upon interacting with negatively charged membranes. D-Cateslytin (D-Ctl), a new epipeptide derived from L-Cateslytin, where all L-amino acids were replaced by D-amino acids. D-Ctl emerges as a potent, safe and robust peptide antimicrobial with undetectable susceptibility to resistance. Using Escherichia coli as a model, D-Ctl targets the bacterial cell wall leading to the permeabilization of the membrane and the death of the bacteria. Overall, D-Ctl offers many assets that make it an attractive candidate for the biopharmaceutical development of new antimicrobials either as a single therapy or as a combination therapy as D-Ctl also has the remarkable property to potentiate several antimicrobials of reference such as cefotaxime, amoxicillin and methicillin.