New Insights into Anthelmintic Mechanisms of Action of a Synthetic Peptide: An Ultrastructural and Nanomechanical Approach

Abstract

Resistant nematodes are not affected by the most common drugs commercially available. In the search for new anthelmintics, peptides have been investigated. Here, a linear synthetic peptide named RcAlb-PepIII bioinspired from the antimicrobial protein Rc-2S-Alb was designed, synthesized, and tested against barber pole worm Haemonchus contortus. The physicochemical properties of the peptide, the 3D structure model, the egg hatch inhibition, and larval development inhibition of H. contortus were carried out. Additionally, the ultrastructure of the nematode after treatment with the peptide was evaluated by atomic force microscopy. The RcAlb-PepIII inhibited the larval development of H. contortus with an EC50 of 90 µM and did not affect egg hatch. Atomic force microscopy reveals the high affinity of RcAlb-PepIII with the cuticle of H. contortus in the L2 stage. It also shows the deposition of RcAlb-PepIII onto the surface of the cuticle, forming a structure similar to a film that reduces the roughness and mean square roughness (Rq) of it. In conclusion, the bioinspired RcAlb-PepIII has the potential to be used as a new anthelmintic compound to control gastrointestinal nematode parasites.

Potent anthelmintic activity of a colloidal nano-silver formulation (Silversol®) against the model worm Caenorhabditis elegans

“…Pimentel-Acosta et al [ 16 ] also reported that silver nanoparticles at high and low concentrations activated dysregulation of similar biological processes (detoxification, neurotoxicity, modulation of cell signaling, embryonic development, reproduction, and tegument organization) by different mechanisms in metazoan parasites of fish. Since cuticle can act as a diffusion barrier for various anthelmintic compounds [ 17 ], combination of silver with conventional anthelmintic agents may allow better penetration of worm body. Silver nano-particles were shown to pass cell membranes and getting internalized in C. elegans by Meyer et al [ 18 ], and they proposed part of the toxicity observed to be mediated by ionic silver.…”

Potent anthelmintic activity of a colloidal nano-silver formulation (Silversol®) against the model worm Caenorhabditis elegans

“…Pimentel-Acosta et al [14] also reported that silver nanoparticles at high and low concentrations activated dysregulation of similar biological processes (detoxi cation, neurotoxicity, modulation of cell signalling, embryonic development, reproduction, and tegument organization) by different mechanisms in metazoan parasites of sh. Since cuticle can act as a diffusion barrier for various anthelmintic compounds [15], combination of silver with conventional anthelmintic agents may allow better penetration of worm body. Silver nano-particles were shown to pass cell membranes and getting internalized in C. elegans by Meyer et al [16], and they proposed part of the toxicity observed to be mediated by ionic silver.…”