When Secretomes Meet Anthelmintics: Lessons for Therapeutic Interventions

• Published in: Trends in parasitology Vol. 37; no. 6; pp. 468 - 475
• Main Authors: Moreno, Yovany, Geary, Timothy G., Tritten, Lucienne
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-06-2021
• Subjects: anthelmintic; drug discovery; helminth; host–parasite interface; secretomes; anthelmintic; helminth; secretomes; host–parasite interface; drug discovery
• ISSN: 1471-4922; 1471-5007
• DOI: 10.1016/j.pt.2021.01.007

Helminth secretomes comprise many potential immunomodulators. The molecular and functional diversity of these entities and their importance at the host–parasite interface have been increasingly recognized. It is now common to hypothesize that parasite-derived molecules (PDMs) are essential mediators used by parasites to establish and remain in their hosts. Suppression of PDM release has been reported for two anthelmintic drug classes, the benzimidazoles and macrocyclic lactones, the mechanisms of action of which remain incompletely resolved. We propose that bringing together recent insights from different streams of parasitology research, for example, immunoparasitology and pharmacology, will stimulate the development of new ways to alter the host–parasite interface in the search for novel anthelmintic strategies.
The molecular negotiations engaged between hosts and parasites have resulted in the evolution of highly specialized interspecific relationships in which an array of PDMs delimit conditions that render the host permissive for the parasite.An underappreciated characteristic of some anthelmintics, such as ivermectin and albendazole, whose mechanisms of action remain incompletely resolved, is their ability to block the release of PDMs in culture.Effects of these drugs on secretion correlate well with the spectrum of activity, kinetics of expulsion, and levels of drug exposure achieved in vivo, as shown experimentally for some parasitic nematodes.Incorporating screens for the inhibition of PDM release in culture as a complement to existing drug discovery efforts may seed novel opportunities in the search for novel anthelmintic strategies.