In vivo and in vitro studies of Cry5B and nicotinic acetylcholine receptor agonist anthelmintics reveal a powerful and unique combination therapy against intestinal nematode parasites

PLoS Neglected Tropical Diseases
Yan HuRaffi V Aroian

Abstract

The soil-transmitted nematodes (STNs) or helminths (hookworms, whipworms, large roundworms) infect the intestines of ~1.5 billion of the poorest peoples and are leading causes of morbidity worldwide. Only one class of anthelmintic or anti-nematode drugs, the benzimidazoles, is currently used in mass drug administrations, which is a dangerous situation. New anti-nematode drugs are urgently needed. Bacillus thuringiensis crystal protein Cry5B is a powerful, promising new candidate. Drug combinations, when properly made, are ideal for treating infectious diseases. Although there are some clinical trials using drug combinations against STNs, little quantitative and systemic work has been performed to define the characteristics of these combinations in vivo. Working with the hookworm Ancylostoma ceylanicum-hamster infection system, we establish a laboratory paradigm for studying anti-nematode combinations in vivo using Cry5B and the nicotinic acetylcholine receptor (nAChR) agonists tribendimidine and pyrantel pamoate. We demonstrate that Cry5B strongly synergizes in vivo with both tribendimidine and pyrantel at specific dose ratios against hookworm infections. For example, whereas 1 mg/kg Cry5B and 1 mg/kg tribendimidine individuall...Continue Reading

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Citations

Sep 14, 2019·The American Journal of Tropical Medicine and Hygiene·Sarit CharuchaibovornSurang Nuchprayoon
Mar 14, 2020·Medicinal Research Reviews·Daniel Sepúlveda-CrespoMaría Martínez-Valladares
Dec 16, 2020·Antimicrobial Agents and Chemotherapy·Hanchen LiRaffi V Aroian
Nov 27, 2020·International Journal for Parasitology. Drugs and Drug Resistance·John SandersRaffi V Aroian
Sep 8, 2021·Parasites & Vectors·Chuanchuan LiuRi-Li Ge

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