High-Throughput Screening of Entamoeba Identifies Compounds Which Target Both Life Cycle Stages and Which Are Effective Against Metronidazole Resistant Parasites

Frontiers in Cellular and Infection Microbiology
Gretchen M EhrenkauferUpinder Singh

Abstract

Neglected tropical diseases, especially those caused by parasites, are significantly underserved by current drug development efforts, mostly due to the high costs and low economic returns. One method for lowering the costs of drug discovery and development for these diseases is to repurpose drugs developed for other indications. Here, we present the results of a screen of five repurposed drug libraries to identify potential new lead compounds to treat amebiasis, a disease that affects tens of millions of people and causes ~100,000 deaths annually. E. histolytica, the causative agent of amebiasis, has two major life cycle stages, the trophozoite and the cyst. The current primary treatment for amebiasis, nitroimidazole compounds, do not eliminate parasites from the colonic lumen, necessitating a multi-drug treatment regimen. We aimed to address this problem by screening against both life stages, with the aim of identifying a single drug that targets both. We successfully identified eleven compounds with activity against both cysts and trophozoites, as well as multiple compounds that killed trophozoites with improved efficacy over existing drugs. Two lead compounds (anisomycin and prodigiosin) were further characterized for activi...Continue Reading

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Citations

Mar 21, 2020·PLoS Neglected Tropical Diseases·Gretchen EhrenkauferUpinder Singh
Sep 16, 2020·BMC Infectious Diseases·Joaquin Alvaro Victoria-HernándezJavier Ventura-Juárez
Feb 9, 2021·PLoS Neglected Tropical Diseases·Conall SauveyRuben Abagyan
Feb 19, 2021·International Journal for Parasitology. Drugs and Drug Resistance·Alexander Y F LamSamantha J Emery-Corbin
Mar 30, 2021·Frontiers in Cellular and Infection Microbiology·Debbie-Ann ShirleyShannon Moonah
Nov 7, 2021·Parasitology Research·Itzia Azucena Rangel-CastañedaJosé Manuel Hernández-Hernández

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Methods Mentioned

BETA
transgenic

Software Mentioned

MetaXpress
MetaExpress
R package drc

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Amoebiasis, infection by the protozoan parasite Entamoeba histolytica, remains a global health problem, despite the availability of effective treatment. Here is the latest research.