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Nat Microbiol. 2016 Jun 13;1(7):16079. doi: 10.1038/nmicrobiol.2016.79.

A global map of genetic diversity in Babesia microti reveals strong population structure and identifies variants associated with clinical relapse.

Author information

1
The Broad Institute of MIT Division of Health Sciences and and MIT, Cambridge 02142, Massachusetts, USA.
2
Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
3
Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
4
Tufts School of Veterinary Medicine, North Grafton, Massachusetts 01536, USA.
5
The Scripps Research Institute, La Jolla, California 92037, USA.
6
Koch Institute for Integrative Cancer Research at MIT, Cambridge, Massachusetts 02142, USA.
7
Department of Pathology, The Mayo Clinic, Rochester, Minnesota 55905, USA.
8
Division of Geographic Medicine and Infectious Disease, Tufts Medical Center, Boston, Massachusetts 02111, USA.
9
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
10
Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
11
Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
12
Department of Evolutionary and Organismic Biology, MIT Division of Health Sciences and University, Cambridge, Massachusetts 02138, USA.

Abstract

Human babesiosis caused by Babesia microti is an emerging tick-borne zoonosis of increasing importance due to its rising incidence and expanding geographic range(1). Infection with this organism, an intraerythrocytic parasite of the phylum Apicomplexa, causes a febrile syndrome similar to malaria(2). Relapsing disease is common among immunocompromised and asplenic individuals(3,4) and drug resistance has recently been reported(5). To investigate the origin and genetic diversity of this parasite, we sequenced the complete genomes of 42 B. microti samples from around the world, including deep coverage of clinical infections at endemic sites in the continental USA. Samples from the continental USA segregate into a Northeast lineage and a Midwest lineage, with subsequent divergence of subpopulations along geographic lines. We identify parasite variants that associate with relapsing disease, including amino acid substitutions in the atovaquone-binding regions of cytochrome b (cytb) and the azithromycin-binding region of ribosomal protein subunit L4 (rpl4). Our results shed light on the origin, diversity and evolution of B. microti, suggest possible mechanisms for clinical relapse, and create the foundation for further research on this emerging pathogen.

PMID:
27572973
PMCID:
PMC5563076
DOI:
10.1038/nmicrobiol.2016.79
[Indexed for MEDLINE]
Free PMC Article

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