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


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.

SUBMITTER: Sa JM 

PROVIDER: S-EPMC6754410 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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

Sá Juliana M JM   Kaslow Sarah R SR   Moraes Barros Roberto R RR   Brazeau Nicholas F NF   Parobek Christian M CM   Tao Dingyin D   Salzman Rebecca E RE   Gibson Tyler J TJ   Velmurugan Soundarapandian S   Krause Michael A MA   Melendez-Muniz Viviana V   Kite Whitney A WA   Han Paul K PK   Eastman Richard T RT   Kim Adam A   Kessler Evan G EG   Abebe Yonas Y   James Eric R ER   Chakravarty Sumana S   Orr-Gonzalez Sachy S   Lambert Lynn E LE   Engels Theresa T   Thomas Marvin L ML   Fasinu Pius S PS   Serre David D   Gwadz Robert W RW   Walker Larry L   DeConti Derrick K DK   Mu Jianbing J   Bailey Jeffrey A JA   Sim B Kim Lee BKL   Hoffman Stephen L SL   Fay Michael P MP   Dinglasan Rhoel R RR   Juliano Jonathan J JJ   Wellems Thomas E TE  

Nature communications 20190920 1


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, m  ...[more]

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