Analysis of mefloquine resistance and amplification of pfmdr1 in multidrug-resistant Plasmodium falciparum isolates from Thailand
- Author(s)
- Chaiyaroj, SC; Buranakiti, A; Ankasekwinai, P; Looareesuwan, S; Cowman, AF;
- Details
- Publication Year 1999-11,Volume 61,Issue #5,Page 780-783
- Journal Title
- AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
- Publication Type
- Journal Article
- Abstract
- Resistance to quinoline-containing compound has been associated with the Plasmodium falciparum multidrug resistance 1 (pfmdr1) gene. We analyzed wild P. falciparum isolates with high levels of chloroquine and mefloquine resistance for their macrorestriction maps of chromosome 5 and sequence of pfmdr1. Two types of chromosome 5 amplification were found, Eleven of 62 resistant isolates displayed Bgl I fragments larger than 100 kb. Twenty-nine isolates possessed multiple copies of the fragments. We failed to detect any amplification of this region on chromosome 5 in 22 mefloquine-resistant isolates, suggesting that other mechanisms can mediate the mefloquine-resistant phenotype. There was no direct association between pfmdr1 mutations and chloroquine sensitivity. Resistant lines could have Asn-86 and Tyr-184 or Phe-184, the predicted sequence of those chloroquine-sensitive isolates. No mutation at Asn-1042 and Asp-1246 was detected among these chloroquine-resistant isolates. Therefore, a few base substitutions in the pfmdr1 gene may not be sufficient to account for all chloroquine-resistant phenotypes.
- Publisher
- AMER SOC TROP MED & HYGIENE
- Keywords
- CHLOROQUINE RESISTANCE; HALOFANTRINE RESISTANCE; CROSS-RESISTANCE; POINT MUTATIONS; IN-VITRO; GENE; MALARIA; OVEREXPRESSION; SENSITIVITY; ASSOCIATION
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- Refer to copyright notice on published article.
Creation Date: 1999-11-01 12:00:00