Malaria: The path of drug resistance

Article Abstract:

In southeast Asia and South America, the parasite Plasmodium falciparum, which causes malaria, has become resistant to chloroquine, the drug most commonly used to treat malaria. The resistant species are slowly spreading beyond these areas. It is not clear how chloroquine works as an anti-malarial drug, but it is thought that chloroquine interferes with the food vacuole of the parasite. It has been shown that chloroquine-resistant parasites can expel the drug, using a protein which functions as a transporter molecule. There have been two recent reports on the significance of this transporter protein in drug resistance in the malarial parasite. A study by Wellems and colleagues examined the presence of the transporter protein in parasites bred from crosses between chloroquine-resistant and chloroquine-sensitive strains. No relationship was found between the sensitivity to chloroquine and the inheritance of the mdr gene, which codes for the transporter molecule. Another study by Foote and colleagues examined mutations, or changes, in the mdr gene which codes for the transporter protein. Mutations were found only in strains that were resistant to chloroquine. A reason for the discrepancy between the two studies could be that many mutations may be needed for drug resistance, so the inheritance of the single mutated transporter gene may not have been sufficient to confer resistance to chloroquine. Further study is needed to identify the other genes and how they interact with the transporter gene. (Consumer Summary produced by Reliance Medical Information, Inc.)

Drug resistance in microorganisms, Microbial drug resistance

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

Article Abstract:

Chloroquine is the drug most frequently used to treat malaria, but in many areas of the world, the parasite Plasmodium falciparum, which causes malaria, has become resistant to chloroquine. It has been shown that chloroquine-resistant parasites can rid themselves of chloroquine, using a protein which functions as a transporter molecule. A similar protein has been identified in the resistance of cancer cells to many different types of drugs; this protein is encoded by the gene mdr. A homologue to mdr has been found in Plasmodium falciparum, and there are multiple copies of the gene in chloroquine-resistant isolates. The genes from different isolates have been sequenced, and mutations, or changes, have been found compared with genes from isolates that are sensitive to chloroquine. However, resistance to chloroquine does not occur as frequently as it would if the resistance was simply due to the inheritance of the one mutated gene. The inheritance of the mutated mdr gene is necessary, but not sufficient, for drug resistance. Therefore, it is thought that more than one gene is needed for the resistance of Plasmodium falciparum to chloroquine to occur. Further study is need to identify the other genes and how they interact with the transporter protein gene. (Consumer Summary produced by Reliance Medical Information, Inc.)

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Chloroquine resistance not linked to mdr-like genes in a Plasmodium falciparum cross

Article Abstract:

In many areas of the world, the parasite Plasmodium falciparum, which causes malaria, has become resistant to chloroquine, the drug most commonly used to treat malaria. The action of chloroquine as an anti-malarial drug is not fully understood, but it is thought that chloroquine interferes with the acid vesicles or food vacuoles of the parasite. Chloroquine-resistant parasites can expel the drug, using a protein which functions as a transporter molecule. A similar protein has been identified which causes resistance to multiple types of drugs in cancer cells. This transporter protein is encoded by the gene mdr. Two genes similar to mdr have been found in Plasmodium falciparum, one of which is thought to be involved in the resistance to chloroquine. Parasites which are progeny from crosses between chloroquine-resistant strains and chloroquine-sensitive strains were developed. The sensitivity of the parasites to chloroquine and the inheritance of the mdr gene were examined. No relationship was found between the sensitivity to chloroquine and the inheritance of the mdr gene, which codes for the transporter molecule. Therefore, it is concluded that genes other than the mdr-like genes must be involved in the resistance to chloroquine. (Consumer Summary produced by Reliance Medical Information, Inc.)

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