Evidence for different mechanisms of chloroquine resistance in 2 Plasmodium species that cause human malaria

Takashi Nomura, Jane M R Carlton, J. Kevin Baird, Hernando A. Del Portillo, David J. Fryauff, Dharmendar Rathore, David A. Fidock, Xin Zhuan Su, William E. Collins, Thomas F. McCutchan, John C. Wootton, Thomas E. Wellems

Research output: Contribution to journalArticle

Abstract

Chloroquine (CQ)-resistant Plasmodium vivax malaria was first reported 12 years ago, nearly 30 years after the recognition of CQ-resistant P. falciparum. Loss of CQ efficacy now poses a severe problem for the prevention and treatment of both diseases. Mutations in a digestive vacuole protein encoded by a 13-exon gene, pfcrt, were shown recently to have a central role in the CQ resistance (CQR) of P. falciparum. Whether mutations in pfcrt orthologues of other Plasmodium species are involved in CQR remains an open question. This report describes pfcrt homologues from P. vivax, P. knowlesi, P. berghei, and Dictyostelium discoideum. Synteny between the P. falciparum and P. vivax genes is demonstrated. However, a survey of patient isolates and monkey-adapted lines has shown no association between in vivo CQR and codon mutations in the P. vivax gene. This is evidence that the molecular events underlying P. vivax CQR differ from those in P. falciparum.

Original languageEnglish (US)
Pages (from-to)1653-1661
Number of pages9
JournalJournal of Infectious Diseases
Volume183
Issue number11
DOIs
StatePublished - Jun 1 2001

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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    Nomura, T., Carlton, J. M. R., Baird, J. K., Del Portillo, H. A., Fryauff, D. J., Rathore, D., Fidock, D. A., Su, X. Z., Collins, W. E., McCutchan, T. F., Wootton, J. C., & Wellems, T. E. (2001). Evidence for different mechanisms of chloroquine resistance in 2 Plasmodium species that cause human malaria. Journal of Infectious Diseases, 183(11), 1653-1661. https://doi.org/10.1086/320707