Mapping of the Plasmodium falciparum multidrug resistance gene 5′-upstream region, and evidence of induction of transcript levels by antimalarial drugs in chloroquine sensitive parasites

SUMMARYHomologues of the mammalian multidrug resistance gene have been identified in isolates and clones of Plasmodium falciparum and designated pfmdr1 and pfmdr2. Mutations in pfmdr1 have been associated with chloroquine resistance but confirmation could not be obtained in a genetic cross. We have examined the copy number and expression of pfmdr1 and pfmdr2 in chloroquine-sensitive and -resistant P. falciparum and have found no relationship between the copy number of either gene and chloroquine resistance. However, a marked correlation was seen between levels of mRNA transcribed for each gene and chloroquine resistance. Two transcripts of pfmdr1 were detected, and in the asexual blood cycle an 8 kb transcript appeared first, followed by the appearance of a 7 kb species.

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Several alleles of the multidrug-resistance gene are closely linked to chloroquine resistance in Plasmodium falciparum

Nature ◽

10.1038/345255a0 ◽

1990 ◽

Vol 345 (6272) ◽

pp. 255-258 ◽

Cited By ~ 378

Author(s):

S. J. Foote ◽

D. E. Kyle ◽

R. K. Martin ◽

A. M. J. Oduola ◽

K. Forsyth ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Multidrug Resistance ◽

Resistance Gene ◽

Chloroquine Resistance ◽

Multidrug Resistance Gene

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Impact of treatment and re-treatment with artemether-lumefantrine and artesunate-amodiaquine on selection of Plasmodium falciparum multidrug resistance gene-1 polymorphisms in the Democratic Republic of Congo and Uganda

PLoS ONE ◽

10.1371/journal.pone.0191922 ◽

2018 ◽

Vol 13 (2) ◽

pp. e0191922 ◽

Cited By ~ 13

Author(s):

Vito Baraka ◽

Hypolite Muhindo Mavoko ◽

Carolyn Nabasumba ◽

Filbert Francis ◽

Pascal Lutumba ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Multidrug Resistance ◽

Resistance Gene ◽

Democratic Republic ◽

Democratic Republic Of Congo ◽

Multidrug Resistance Gene ◽

Republic Of Congo ◽

Selection Of

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Allele-specific, nested, one tube PCR: application to Pfmdr1 polymorphisms in Plasmodium falciparum

Parasitology ◽

10.1017/s0031182099004382 ◽

1999 ◽

Vol 119 (1) ◽

pp. 1-6 ◽

Cited By ~ 9

Author(s):

I. S. ADAGU ◽

D. C. WARHURST

Keyword(s):

Plasmodium Falciparum ◽

Multidrug Resistance ◽

Single Nucleotide Polymorphisms ◽

Resistance Gene ◽

Point Mutations ◽

Nucleotide Polymorphisms ◽

Multidrug Resistance Gene ◽

Single Nucleotide ◽

Reliable Detection ◽

Allele Specific

An allele-specific, one tube PCR for the sensitive and reliable detection of point mutations in Plasmodium falciparum DNA is described. Design of specific internal primers and optimization of the PCR is simple, and the procedure is robust and sensitive. Single nucleotide polymorphisms at codons 184, 1034, 1042 and 1246 of the P. falciparum multidrug resistance gene Pfmdr1, were examined in 6 laboratory isolates, to validate the technique.

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