Plasmodium falciparum: the calmodulin gene is not amplified or overexpressed in chloroquine resistant or sensitive isolates.
The in vitro growth of Plasmodium falciparum is sensitive to some calmodulin antagonists and these compounds show antagonism with classic antimalarials such as chloroquine suggesting competition for the same drug binding site. In order to ask if calmodulin is involved in resistance to chloroquine we cloned the calmodulin gene of P. falciparum. We show that it is encoded by a single gene and that the putative protein is highly homologous to calmodulin from other eukaryotes. The calmodulin gene is encoded on chromosome 14 and contains a single intron of 506 bp that has the appropriate donor and acceptor splice sites. Two major transcripts of similar size are encoded by this gene. The sequence of the gene is identical and the calmodulin protein is expressed approximately equally in chloroquine resistant and sensitive isolates of P. falciparum suggesting that alterations in this protein play no role in the mechanism of chloroquine resistance in the isolates tested.
Cowman
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AF
Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
Galatis
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D
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002147:Calmodulin / Q000096:biosynthesis / Q000235:genetics*; D002738:Chloroquine / Q000494:pharmacology*; D002874:Chromosome Mapping; D016054:DNA, Protozoan / Q000235:genetics; D004351:Drug Resistance; D005784:Gene Amplification; D015870:Gene Expression; D005796:Genes; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D014158:Transcription, Genetic
D002147:Calmodulin; D016054:DNA, Protozoan; D002738:Chloroquine