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J Biol Chem. 2018 Dec 28;293(52):19974-19981. doi: 10.1074/jbc.AC118.005771. Epub 2018 Nov 21.

Establishment of a continuous in vitro culture of Babesia duncani in human erythrocytes reveals unusually high tolerance to recommended therapies.

Author information

1
From the Department of Internal Medicine, Section of Infectious Diseases, and.
2
BEI Resources, American Type Culture Collection, Manassas, Virginia 20110-2209.
3
the State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430079, China, and.
4
the Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas 77845.
5
the Department of Cell Biology and CCMI Electron Microscopy Core Facility, Yale School of Medicine, New Haven, Connecticut 06520.
6
From the Department of Internal Medicine, Section of Infectious Diseases, and choukri.benmamoun@yale.edu.

Abstract

Human babesiosis is an emerging tick-borne disease caused by apicomplexan parasites of the genus Babesia Clinical cases caused by Babesia duncani have been associated with high parasite burden, severe pathology, and death. In both mice and hamsters, the parasite causes uncontrolled fulminant infections, which ultimately lead to death. Resolving these infections requires knowledge of B. duncani biology, virulence, and susceptibility to anti-infectives, but little is known and further research is hindered by a lack of relevant model systems. Here, we report the first continuous in vitro culture of B. duncani in human red blood cells. We show that during its asexual cycle within human erythrocytes, B. duncani develops and divides to form four daughter parasites with parasitemia doubling every ∼22 h. Using this in vitro culture assay, we found that B. duncani has low susceptibility to the four drugs recommended for treatment of human babesiosis, atovaquone, azithromycin, clindamycin, and quinine, with IC50 values ranging between 500 nm and 20 μm These data suggest that current practices are of limited effect in treating the disease. We anticipate this new disease model will set the stage for a better understanding of the biology of this parasite and will help guide better therapeutic strategies to treat B. duncani-associated babesiosis.

KEYWORDS:

Babesia duncani; apicomplexa; cell culture; erythrocyte; human babesiosis; in vitro culture; infectious disease; inhibitor; parasitology; red blood cells; tick-borne disease

PMID:
30463941
PMCID:
PMC6311517
[Available on 2019-12-28]
DOI:
10.1074/jbc.AC118.005771
[Indexed for MEDLINE]

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