UMMS Affiliation
Program in Bioinformatics and Integrative Biology; Division of Transfusion Medicine, Department of Medicine
Publication Date
2019-09-20
Document Type
Article
Disciplines
Computational Biology | Immunology and Infectious Disease | Parasitic Diseases | Population Biology
Abstract
Mainstay treatment for Plasmodium vivax malaria has long relied on chloroquine (CQ) against blood-stage parasites plus primaquine against dormant liver-stage forms (hypnozoites), however drug resistance confronts this regimen and threatens malaria control programs. Understanding the basis of P. vivax chloroquine resistance (CQR) will inform drug discovery and malaria control. Here we investigate the genetics of P. vivax CQR by a cross of parasites differing in drug response. Gametocytogenesis, mosquito infection, and progeny production are performed with mixed parasite populations in nonhuman primates, as methods for P. vivax cloning and in vitro cultivation remain unavailable. Linkage mapping of progeny surviving > 15 mg/kg CQ identifies a 76 kb region in chromosome 1 including pvcrt, an ortholog of the Plasmodium falciparum CQR transporter gene. Transcriptional analysis supports upregulated pvcrt expression as a mechanism of CQR.
Keywords
Antimicrobial resistance, Antiparasitic agents, Malaria, Parasite genetics
Rights and Permissions
Copyright © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
DOI of Published Version
10.1038/s41467-019-12256-9
Source
Nat Commun. 2019 Sep 20;10(1):4300. doi: 10.1038/s41467-019-12256-9. Link to article on publisher's site
Journal/Book/Conference Title
Nature communications
Related Resources
PubMed ID
31541097
Repository Citation
Sa JM, DeConti DK, Bailey JA, Wellems TE. (2019). Plasmodium vivax chloroquine resistance links to pvcrt transcription in a genetic cross. Open Access Articles. https://doi.org/10.1038/s41467-019-12256-9. Retrieved from https://escholarship.umassmed.edu/oapubs/3997
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Included in
Computational Biology Commons, Immunology and Infectious Disease Commons, Parasitic Diseases Commons, Population Biology Commons
Comments
Full author list omitted for brevity. For the full list of authors, see article.