AJTMH ASTMH MEMBERSHIP INFORMATION: astmh@astmh.org
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am. J. Trop. Med. Hyg., 51(5), 1994, pp. 648-658
Copyright © 1994 by The American Society of Tropical Medicine and Hygiene

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Peel, S. A.
Right arrow Articles by Baric, R. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Peel, S. A.
Right arrow Articles by Baric, R. S.

A Strong Association between Mefloquine and Halofantrine Resistance and Amplification, Overexpression, and Mutation in the P-Glycoprotein Gene Homolog (pfmdr) of Plasmodium falciparum In Vitro

Sheila A. Peel, Patricia Bright, Boyd Yount, Jean Handy AND Ralph S. Baric
Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

Stepwise selection for increased mefloquine resistance in a line of Plasmodium falciparum in vitro resulted in increased resistance to halofantrine and quinine, increased sensitivity to chloroquine, and amplification and overexpression of the P-glycoprotein gene homolog (pfmdr1). A point mutation (tyrosine to phenylalanine) noted at amino acid 86 in pfmdr1 in the mefloquine-resistant line W2mef was amplified in more resistant lines derived from it by in vitro selection pressure with mefloquine. Conversely, lines selected for increased chloroquine resistance exhibited a revertant phenotype that was sensitive to mefloquine and halofantrine. These lines also demonstrated increased sensitivity to quinine, loss of amplification of pfmdr1, loss of the mefloquine/halofantrine phenylalanine-86 mutation, and selection for a tyrosine-86 mutation previously associated with chloroquine resistance. These findings provide strong evidence for pfmdr1 mediating cross-resistance to halofantrine and mefloquine in P. falciparum in vitro.




This article has been cited by other articles:


Home page
 Antimicrob. Agents Chemother.Home page
P. Preechapornkul, M. Imwong, K. Chotivanich, W. Pongtavornpinyo, A. M. Dondorp, N. P. J. Day, N. J. White, and S. Pukrittayakamee
Plasmodium falciparum pfmdr1 Amplification, Mefloquine Resistance, and Parasite Fitness
Antimicrob. Agents Chemother., April 1, 2009; 53(4): 1509 - 1515.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
M. Imwong, S. Pukrittayakamee, W. Pongtavornpinyo, S. Nakeesathit, S. Nair, P. Newton, F. Nosten, T. J. C. Anderson, A. Dondorp, N. P. J. Day, et al.
Gene Amplification of the Multidrug Resistance 1 Gene of Plasmodium vivax Isolates from Thailand, Laos, and Myanmar
Antimicrob. Agents Chemother., July 1, 2008; 52(7): 2657 - 2659.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
D. J. Johnson, A. Owen, N. Plant, P. G. Bray, and S. A. Ward
Drug-Regulated Expression of Plasmodium falciparum P-Glycoprotein Homologue 1: a Putative Role for Nuclear Receptors
Antimicrob. Agents Chemother., April 1, 2008; 52(4): 1438 - 1445.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
S. Nair, D. Nash, D. Sudimack, A. Jaidee, M. Barends, A.-C. Uhlemann, S. Krishna, F. Nosten, and T. J. C. Anderson
Recurrent Gene Amplification and Soft Selective Sweeps during Evolution of Multidrug Resistance in Malaria Parasites
Mol. Biol. Evol., February 1, 2007; 24(2): 562 - 573.
[Abstract] [Full Text] [PDF]

Home page
 J Clin PharmacolHome page
J. P. Daily
Antimalarial drug therapy: the role of parasite biology and drug resistance.
J. Clin. Pharmacol., December 1, 2006; 46(12): 1487 - 1497.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Microbiol.Home page
B. Pradines, P. Hovette, T. Fusai, H. L. Atanda, E. Baret, P. Cheval, J. Mosnier, A. Callec, J. Cren, R. Amalvict, et al.
Prevalence of In Vitro Resistance to Eleven Standard or New Antimalarial Drugs among Plasmodium falciparum Isolates from Pointe-Noire, Republic of the Congo.
J. Clin. Microbiol., July 1, 2006; 44(7): 2404 - 2408.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Singh and P. J. Rosenthal
Selection of Cysteine Protease Inhibitor-resistant Malaria Parasites Is Accompanied by Amplification of Falcipain Genes and Alteration in Inhibitor Transport
J. Biol. Chem., August 20, 2004; 279(34): 35236 - 35241.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. L. Waller, R. A. Muhle, L. M. Ursos, P. Horrocks, D. Verdier-Pinard, A. B. S. Sidhu, H. Fujioka, P. D. Roepe, and D. A. Fidock
Chloroquine Resistance Modulated in Vitro by Expression Levels of the Plasmodium falciparum Chloroquine Resistance Transporter
J. Biol. Chem., August 29, 2003; 278(35): 33593 - 33601.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 1994 by the American Society of Tropical Medicine and Hygiene.