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Multiple transporters associated with malaria parasite responses to chloroquine and quinine
Molecular Microbiology (2003)
  • Jianbing Mu, Laboratory of Malaria and Vector Research, National Institutes of Health
  • Michael T. Ferdig, Department of Biological Sciences, University of Notre Dame
  • Xiaorong Feng, Laboratory of Malaria and Vector Research, National Institutes of Health
  • Deirdre A. Joy, Laboratory of Malaria and Vector Research, National Institutes of Health
  • Junhui Duan, Laboratory of Malaria and Vector Research, National Institutes of Health
  • Tetsuya Furuya, Laboratory of Malaria and Vector Research, National Institutes of Health
  • G. Subramanian, Human Genome Sciences
  • L. Aravind, National Center for Biotechnology Information, National Institutes of Health
  • Roland A. Cooper, Department of Biological Sciences, Old Dominion University
  • John C. Wootton, National Center for Biotechnology Information, National Institutes of Health
  • Momiao Xiong, Human Genetics Center, University of Texas
  • Xin-zhuan Su, Laboratory of Malaria and Vector Research, National Institutes of Health
Abstract
Mutations and/or overexpression of various transporters are known to confer drug resistance in a variety of organisms. In the malaria parasite Plasmodium falciparum, a homologue of P-glycoprotein, PfMDR1, has been implicated in responses to chloroquine (CQ), quinine (QN) and other drugs, and a putative transporter, PfCRT, was recently demonstrated to be the key molecule in CQ resistance. However, other unknown molecules are probably involved, as different parasite clones carrying the same pfcrt and pfmdr1 alleles show a wide range of quantitative responses to CQ and QN. Such molecules may contribute to increasing incidences of QN treatment failure, the molecular basis of which is not understood. To identify additional genes involved in parasite CQ and QN responses, we assayed the in vitro susceptibilities of 97 culture-adapted cloned isolates to CQ and QN and searched for single nucleotide polymorphisms (SNPs) in DNA encoding 49 putative transporters (total 113 kb) and in 39 housekeeping genes that acted as negative controls. SNPs in 11 of the putative transporter genes, including pfcrt and pfmdr1, showed significant associations with decreased sensitivity to CQ and/or QN in P. falciparum. Significant linkage disequilibria within and between these genes were also detected, suggesting interactions among the transporter genes. This study provides specific leads for better understanding of complex drug resistances in malaria parasites.
Disciplines
Publication Date
August, 2003
Citation Information
Jianbing Mu, Michael T. Ferdig, Xiaorong Feng, Deirdre A. Joy, et al.. "Multiple transporters associated with malaria parasite responses to chloroquine and quinine" Molecular Microbiology Vol. 49 Iss. 4 (2003) p. 977 - 989 ISSN: 0950-382X
Available at: http://works.bepress.com/roland_cooper/14/