Experimental evolution of resistance to artemisinin combination therapy results in amplification of the mdr1 gene in a rodent malaria parasite.

PloS One
Louise A RodriguesP Cravo

Abstract

Lacking suitable alternatives, the control of malaria increasingly depends upon Artemisinin Combination Treatments (ACT): resistance to these drugs would therefore be disastrous. For ACTs, the biology of resistance to the individual components has been investigated, but experimentally induced resistance to component drugs in combination has not been generated. We have used the rodent malaria parasite Plasmodium chabaudi to select in vivo resistance to the artesunate (ATN)+mefloquine (MF) version of ACT, through prolonged exposure of parasites to both drugs over many generations. The selection procedure was carried out over twenty-seven consecutive sub-inoculations under increasing ATN+MF doses, after which a genetically stable resistant parasite, AS-ATNMF1, was cloned. AS-ATNMF1 showed increased resistance to ATN+MF treatment and to artesunate or mefloquine administered separately. Investigation of candidate genes revealed an mdr1 duplication in the resistant parasites and increased levels of mdr1 transcripts and protein. There were no point mutations in the atpase6 or ubp1genes. Resistance to ACTs may evolve even when the two drugs within the combination are taken simultaneously and amplification of the mdr1 gene may contribut...Continue Reading

References

Jul 1, 1992·British Journal of Clinical Pharmacology·N J White
Aug 1, 1991·International Journal of Radiation Oncology, Biology, Physics·P M HarariJ R Cassady
Nov 25, 1988·Nucleic Acids Research·F Corpet
Feb 1, 1994·Proceedings of the National Academy of Sciences of the United States of America·A F CowmanJ K Thompson
Feb 17, 1998·Transactions of the Royal Society of Tropical Medicine and Hygiene·R N PriceN J White
Jun 12, 1999·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·N White
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Jul 18, 2002·Antimicrobial Agents and Chemotherapy·Karen HaytonDavid Walliker
Jan 25, 2003·Antimicrobial Agents and Chemotherapy·Pedro V L CravoDavid Walliker
Aug 22, 2003·Nature·U Eckstein-LudwigS Krishna
Aug 24, 2004·Molecular Pharmacology·Zhigang ZhangJin-Ming Yang
Feb 1, 2005·Tropical Medicine & International Health : TM & IH·Shunmay Yeung, Nicholas J White
Jun 7, 2005·Nature Structural & Molecular Biology·Anne-Catrin UhlemannSanjeev Krishna
Mar 7, 2006·Nature Reviews. Drug Discovery·Gergely SzakácsMichael M Gottesman
May 3, 2006·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Ric N PriceFrançois Nosten
Jul 31, 2009·The New England Journal of Medicine·Arjen M DondorpNicholas J White
Jul 31, 2009·The New England Journal of Medicine·Harald NoedlWichai Satimai
Nov 4, 2009·Expert Review of Anti-infective Therapy·Patricia Schlagenhauf, Eskild Petersen
Nov 13, 2009·Malaria Journal·Nicholas J WhiteNicholas P J Day

❮ Previous
Next ❯

Citations

Mar 1, 2012·Journal of Pharmacy & Bioallied Sciences·Cristopher A BoyaMarcelino Gutierrez
May 4, 2011·Malaria Journal·Ana Carolina A V KayanoFabio T M Costa
Sep 28, 2012·Proceedings. Biological Sciences·Petra SchneiderSarah E Reece
Aug 13, 2013·Vector Borne and Zoonotic Diseases·Kaliyaperumal KarunamoorthiJayaraman Vijayalakshmi
Jan 7, 2015·Proceedings of the National Academy of Sciences of the United States of America·Mostafa A ElfawalStephen M Rich
Dec 21, 2010·Trends in Parasitology·Xavier C DingGiovanna Raso
Jul 21, 2012·Molecular Microbiology·Long CuiLiwang Cui
Nov 16, 2011·Antimicrobial Agents and Chemotherapy·Matthew S TuckerDennis E Kyle

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
ubiquitination
Precipitation

Software Mentioned

Multi
Align

Related Concepts

Related Feeds

Antimicrobial Resistance (ASM)

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Antimicrobial Resistance

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Antimalarial Agents (ASM)

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.

Addiction

This feed focuses mechanisms underlying addiction and addictive behaviour including heroin and opium dependence, alcohol intoxication, gambling, and tobacco addiction.

Antimalarial Agents

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.