Plasmodium vivax chloroquine resistance links to pvcrt transcription in a genetic cross

Sa, Juliana M.; DeConti, Derrick K.; Bailey, Jeffrey A.; Wellems, Thomas E.

dc.contributor.author	Sa, Juliana M.
dc.contributor.author	DeConti, Derrick K.
dc.contributor.author	Bailey, Jeffrey A.
dc.contributor.author	Wellems, Thomas E.
dc.date	2022-08-11T08:09:54.000
dc.date.accessioned	2022-08-23T16:48:07Z
dc.date.available	2022-08-23T16:48:07Z
dc.date.issued	2019-09-20
dc.date.submitted	2019-10-27
dc.identifier.citation	<p>Nat Commun. 2019 Sep 20;10(1):4300. doi: 10.1038/s41467-019-12256-9. <a href="https://doi.org/10.1038/s41467-019-12256-9">Link to article on publisher's site</a></p>
dc.identifier.issn	2041-1723 (Linking)
dc.identifier.doi	10.1038/s41467-019-12256-9
dc.identifier.pmid	31541097
dc.identifier.uri	http://hdl.handle.net/20.500.14038/41210
dc.description	<p>Full author list omitted for brevity. For the full list of authors, see article.</p>
dc.description.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.
dc.language.iso	en_US
dc.relation	<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=31541097&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rights	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/.
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/
dc.subject	Antimicrobial resistance
dc.subject	Antiparasitic agents
dc.subject	Malaria
dc.subject	Parasite genetics
dc.subject	Computational Biology
dc.subject	Immunology and Infectious Disease
dc.subject	Parasitic Diseases
dc.subject	Population Biology
dc.title	Plasmodium vivax chloroquine resistance links to pvcrt transcription in a genetic cross
dc.type	Journal Article
dc.source.journaltitle	Nature communications
dc.source.volume	10
dc.source.issue	1
dc.identifier.legacyfulltext	https://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=5014&context=oapubs&unstamped=1
dc.identifier.legacycoverpage	https://escholarship.umassmed.edu/oapubs/3997
dc.identifier.contextkey	15631396
refterms.dateFOA	2022-08-23T16:48:07Z
html.description.abstract	<p>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.</p>
dc.identifier.submissionpath	oapubs/3997
dc.contributor.department	Division of Transfusion Medicine, Department of Medicine
dc.contributor.department	Program in Bioinformatics and Integrative Biology
dc.source.pages	4300

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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/.

Except where otherwise noted, this item's license is described as 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/.