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

Amplification, mutations, or overexpression of the pfmdr1 gene have been as sociated with multiple drug resistance in some strains of Plasmodium falcip arum. In order to better understand this potential mechanism of drug resist ance, we are currently investigating putative mdr homologues in vivo in the rodent malaria Plasmodium berghei. We have identified and partially sequen ced a gene that is amplified in a MFQ-resistant (MFQ(r)) line. Using degene rate primers, a 579-bp fragment was amplified by PCR using P. berghei genom ic DNA as template. The predicted amino acid sequence shares 66% identity w ith the previously reported pfmdr1 gene product (Pgh1) of P. falciparum. So uthern blots and slot blots of genomic DNA suggest that this gene is amplif ied two- to threefold in a MFQ(r) line (N/1100), as has been previously rep orted in some MFQ(r) strains of P. falciparum. The P. berghei gene was mapp ed to chromosome 12 in all of the lines analyzed. Furthermore, the cloned P CR product also hybridizes to chromosome 5 of the MFQ(r) strain. (C) 1999 A cademic Press.