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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Wollenberg, Kurt Moss, Eli Nguitragool, Wang Zainabadi, Kayvan Galinsky, Kevin Sellers, Morgan Neafsey, Daniel Desai, Sanjay A. Sharma, Paresh |
| Description | Author Affiliation: Sharma P ( Laboratory of Malaria and Vector Research, Office of Cyber Infrastructure and Computational Biology, NIAID, National Institutes of Health, Bethesda, Maryland 20852, USA.) |
| Abstract | Acquired antimalarial drug resistance produces treatment failures and has led to periods of global disease resurgence. In Plasmodium falciparum, resistance is known to arise through genome-level changes such as mutations and gene duplications. We now report an epigenetic resistance mechanism involving genes responsible for the plasmodial surface anion channel, a nutrient channel that also transports ions and antimalarial compounds at the host erythrocyte membrane. Two blasticidin S-resistant lines exhibited markedly reduced expression of clag genes linked to channel activity, but had no genome-level changes. Silencing aborted production of the channel protein and was directly responsible for reduced uptake. Silencing affected clag paralogs on two chromosomes and was mediated by specific histone modifications, allowing a rapidly reversible drug resistance phenotype advantageous to the parasite. These findings implicate a novel epigenetic resistance mechanism that involves reduced host cell uptake and is a worrisome liability for water-soluble antimalarial drugs. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 27 |
| Volume Number | 288 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2013-07-05 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Drug Resistance Epigenesis, Genetic Genes, Protozoan Malaria, Falciparum Metabolism Plasmodium Falciparum Protozoan Proteins Antimalarials Therapeutic Use Antiporters Genetics Cell Adhesion Molecules Enzyme Inhibitors Pharmacology Ion Transport Drug Effects Drug Therapy Nucleosides Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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