Plasmodium berghei: identification of an mdr-like gene associated with drug resistance.

Amplification, mutations, or overexpression of the pfmdr1 gene have been associated with multiple drug resistance in some strains of Plasmodium falciparum. In order to better understand this potential mechanism of drug resistance, we are currently investigating putative mdr homologues in vivo in the rodent malaria Plasmodium berghei. We have identified and partially sequenced a gene that is amplified in a MFQ-resistant (MFQr) line. Using degenerate primers, a 579-bp fragment was amplified by PCR using P. berghei genomic DNA as template. The predicted amino acid sequence shares 66% identity with the previously reported pfmdr1 gene product (Pgh1) of P. falciparum. Southern blots and slot blots of genomic DNA suggest that this gene is amplified two- to threefold in a MFQr line (N/1100), as has been previously reported in some MFQr strains of P. falciparum. The P. berghei gene was mapped to chromosome 12 in all of the lines analyzed. Furthermore, the cloned PCR product also hybridizes to chromosome 5 of the MFQr strain.