Plasmodium vivax chloroquine resistance links to pvcrt transcription in a genetic cross.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31541097.
- Also identified by DOI 10.1038/s41467-019-12256-9 and PMC identifier 6754410.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Antimalarials
- Chloroquine
- Crosses, Genetic
- Drug Resistance
- Membrane Transport Proteins
- Plasmodium vivax
- Protozoan Proteins