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

by Salzman, Rebecca E. , Wellems, Thomas E. , Han, Paul K. , Melendez-Muniz, Viviana , Sá, Juliana M. , Kaslow, Sarah R. , Tao, Dingyin , James, Eric R. , Orr-Gonzalez, Sachy , Dinglasan, Rhoel R. , Kessler, Evan G. , Brazeau, Nicholas F. , Moraes Barros, Roberto R. , Chakravarty, Sumana , Engels, Theresa , DeConti, Derrick K. , Fasinu, Pius S. , Mu, Jianbing , Gibson, Tyler J. , Bailey, Jeffrey A. , Sim, B. Kim Lee , Fay, Michael P. , Thomas, Marvin L. , Velmurugan, Soundarapandian , Krause, Michael A. , Gwadz, Robert W. , Juliano, Jonathan J. , Walker, Larry , Lambert, Lynn E. , Parobek, Christian M. , Hoffman, Stephen L. , Kim, Adam , Kite, Whitney A. , Serre, David , Eastman, Richard T. , Abebe, Yonas

in 38/77 / 45/22 / 45/88 / 49/23 / 631/326/22/1294 / 631/326/22/1434 / 631/326/417/2550 / 692/699/255/1629 / 82/58 / Animals / Anopheles - parasitology / Antimalarials - pharmacology / Chloroquine / Chloroquine - pharmacology / Chromosome 1 / Chromosomes / Cloning / Control programs / Crosses, Genetic / Culicidae - parasitology / Cultivation / Drug Discovery / Drug resistance / Drug Resistance - genetics / Female / Gene Expression / Gene mapping / Genes, Protozoan / Genetic crosses / Genetics / Humanities and Social Sciences / Malaria / Malaria - drug therapy / Malaria, Vivax - drug therapy / Malaria, Vivax - parasitology / Male / Mapping / Membrane Transport Proteins - genetics / multidisciplinary / Parasites / Plasmodium falciparum - genetics / Plasmodium vivax / Plasmodium vivax - drug effects / Plasmodium vivax - genetics / Primaquine / Primates / Progeny / Protozoan Proteins - genetics / Science / Science (multidisciplinary) / Transcription / Vector-borne diseases

2019

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

2019

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2019

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Journal Article

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

Salzman, Rebecca E.,

Wellems, Thomas E.,

Han, Paul K.,

Melendez-Muniz, Viviana,

Sá, Juliana M.,

Kaslow, Sarah R.,

Tao, Dingyin,

James, Eric R.,

Orr-Gonzalez, Sachy,

Dinglasan, Rhoel R.,

Kessler, Evan G.,

Brazeau, Nicholas F.,

Moraes Barros, Roberto R.,

Chakravarty, Sumana,

Engels, Theresa,

DeConti, Derrick K.,

Fasinu, Pius S.,

Mu, Jianbing,

Gibson, Tyler J.,

Bailey, Jeffrey A.,

Sim, B. Kim Lee,

Fay, Michael P.,

Thomas, Marvin L.,

Velmurugan, Soundarapandian,

Krause, Michael A.,

Gwadz, Robert W.,

Juliano, Jonathan J.,

Walker, Larry,

Lambert, Lynn E.,

Parobek, Christian M.,

Hoffman, Stephen L.,

Kim, Adam,

Kite, Whitney A.,

Serre, David,

Eastman, Richard T.,

Abebe, Yonas

2019

Overview

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. Here, a cross of Plasmodium vivax malaria parasites links a chloroquine resistance (CQR) phenotype to a 76 kb region of chromosome 1 and greater expression of pvcrt , an ortholog of the Plasmodium falciparum CQR transporter gene.

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Publisher

Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio

Subject

38/77

/ 45/22

/ 45/88

/ 49/23

/ 631/326/22/1294

/ 631/326/22/1434

/ 631/326/417/2550