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Int J Parasitol. 2019 Feb;49(2):105-113. doi: 10.1016/j.ijpara.2018.05.008. Epub 2018 Aug 31.

Insights into the evolution and drug susceptibility of Babesia duncani from the sequence of its mitochondrial and apicoplast genomes.

Author information

1
Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, CT 06520, USA.
2
Department of Statistics, University of California, 900 University Avenue, Riverside, CA 92521, USA.
3
Department of Genetics, Yale School of Medicine, New Haven, CT 06520, USA.
4
Department of Biology, San Francisco State University, 1600 Holloway Ave, San Francisco, CA 94132, USA.
5
Department of Cell Biology & Neuroscience, 900 University Avenue, University of California, Riverside, CA 92521, USA.
6
Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, CT 06520, USA. Electronic address: choukri.benmamoun@yale.edu.

Abstract

Babesia microti and Babesia duncani are the main causative agents of human babesiosis in the United States. While significant knowledge about B. microti has been gained over the past few years, nothing is known about B. duncani biology, pathogenesis, mode of transmission or sensitivity to currently recommended therapies. Studies in immunocompetent wild type mice and hamsters have shown that unlike B. microti, infection with B. duncani results in severe pathology and ultimately death. The parasite factors involved in B. duncani virulence remain unknown. Here we report the first known completed sequence and annotation of the apicoplast and mitochondrial genomes of B. duncani. We found that the apicoplast genome of this parasite consists of a 34 kb monocistronic circular molecule encoding functions that are important for apicoplast gene transcription as well as translation and maturation of the organelle's proteins. The mitochondrial genome of B. duncani consists of a 5.9 kb monocistronic linear molecule with two inverted repeats of 48 bp at both ends. Using the conserved cytochrome b (Cytb) and cytochrome c oxidase subunit I (coxI) proteins encoded by the mitochondrial genome, phylogenetic analysis revealed that B. duncani defines a new lineage among apicomplexan parasites distinct from B. microti, Babesia bovis, Theileria spp. and Plasmodium spp. Annotation of the apicoplast and mitochondrial genomes of B. duncani identified targets for development of effective therapies. Our studies set the stage for evaluation of the efficacy of these drugs alone or in combination against B. duncani in culture as well as in animal models.

KEYWORDS:

Annotation; Apicoplast; Babesiosis; Drug targets; Genome; Mitochondria; Sequencing

PMID:
30176236
PMCID:
PMC6395566
[Available on 2020-02-01]
DOI:
10.1016/j.ijpara.2018.05.008

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