Molecular Characterization of Mefloquine Resistance in Plasmodium Falciparum

摘要

The molecular basis for mefloquine resistance in the human malaria parasite,Plasmodium falciparum was investigated using recombinant DNA techniques. The parasites were found to be capable of manifesting extremely high levels of resistance to the drug in vitro. Resistant lines were found to be rapidly growing, impervious to various treatments, and significantly stimulated to grow by low levels of mefloquine. At the molecular levels, it was found that the genes for tubulin, a calmodulin-like protein, and a P-glycoprotein-like protein were all amplified in a quantitative relationship to the degree of resistance. Clones for each of these genes were isolated and characterized. Attempts were made to induce the amplification of tubulin genes in a sensitive parasite to see whether this event would confer resistance. High levels of vinblastine resistance were achieved but without evidence of gene amplification. Hence, the exact relationship between the amplification event and drug resistance remains unresolved. Keywords: Biotechnology; DNA structure; Drugs; Infectious diseases; Malaria; Mefloquine; Plasmodium; Parasitology. (jes)