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Antimicrobial Agents and Chemotherapy, December 2004, p. 4869-4872, Vol. 48, No. 12
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.12.4869-4872.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Polymorphism in Plasmodium falciparum Drug Transporter Proteins and Reversal of In Vitro Chloroquine Resistance by a 9,10-Dihydroethanoanthracene Derivative

Julie Millet,1,2 Sandrine Alibert,2,3 Marylin Torrentino-Madamet,1,2 Christophe Rogier,1,2 Christiane Santelli-Rouvier,2,3 Patricia Bigot,1,2 Joel Mosnier,1,2 Eric Baret,1,2 Jacques Barbe,2,3 Daniel Parzy,1,2 and Bruno Pradines1,3*

Unité de Parasitologie, Institut de Médecine Tropicale du Service de Santé des Armées,1 GERCTOP-UMR CNRS 6009, Faculté de Pharmacie,3 Institut Fédératif de la Recherche 482

Received 10 June 2004/ Returned for modification 9 July 2004/ Accepted 12 August 2004

BG958 reverses resistance in chloroquine-resistant isolates from different countries. Five mutations in the Plasmodium falciparum crt (pfcrt) gene resulting in the amino acid changes K76T, M74I, N75E, A220S, and R371I are systematically identified in resistance-reversed Asian, African, and Brazilian parasites which possess the pfcrt (CIET) haplotype. In combination with BG958, the activity of chloroquine is increased in parasites with the N86Y mutation in pfmdr1.

* Corresponding author. Mailing address: IMTSSA, Unité de Parasitologie, Bd. Charles Livon, Parc le Pharo, BP 46, 13998 Marseille Armées, France. Phone: 33 4 91 15 01 10. Fax: 33 4 91 15 01 64. E-mail: bruno.pradines{at}free.fr.

Antimicrobial Agents and Chemotherapy, December 2004, p. 4869-4872, Vol. 48, No. 12
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.12.4869-4872.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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