Babesia duncani as a Model Organism to Study the Development, Virulence, and Drug Susceptibility of Intraerythrocytic Parasites In Vitro and In Vivo
Abstract
Human babesiosis is a malaria-like illness caused by tick-borne intraerythrocytic Babesia parasites of the Apicomplexa phylum. Whereas several species of Babesia can cause severe disease in humans, the ability to propagate Babesia duncani both in vitro in human erythrocytes and in mice makes it a unique pathogen to study Babesia biology and pathogenesis. Here we report an optimized B. duncani in culture–in mouse (ICIM) model that combines continuous in vitro culture of the parasite with a precise model of lethal infection in mice. We demonstrate that B. duncani–infected erythrocytes as well as free merozoites can cause lethal infection in C3H/HeJ mice. Highly reproducible parasitemia and survival outcomes could be established using specific parasite loads in different mouse genetic backgrounds. Using the ICIM model, we discovered 2 new endochin-like quinolone prodrugs (ELQ-331 and ELQ-468) that alone or in combination with atovaquone are highly efficacious against B. duncani and Babesia microti.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 04, 2022
- Source ID
- 10.1093/infdis/jiac181
Entities
People
- Aaron C. Nilsen
- Anasuya C. Pal
- Choukri Ben Mamoun
- Isaline Renard
- J Stone Doggett
- Joy E. Chiu
- Lisa Frueh
- Michael K. Riscoe
- Pallavi Singh
- Pratap Vydyam
- Rolf W. Winter
- Rozalia A Dodean
- Sovitj Pou
Organizations
- Global Lyme Alliance
- National Institutes of Health
- Steven & Alexandra Cohen Foundation
- United States Department of Defense
- United States Department of Veterans Affairs
- Veterans Health Administration
- Veterans Health Administration Office of Research and Development
- Yale School of Medicine