Mechanisms of Drug Resistance in Plasmodium falciparum
Abstract
Drug resistance has emerged as a major problem in the treatment of all microbial agents and in many cancer chemotherapies. This has necessitated the continuous development of new chemotherapeutic agents both for treatment of infectious agents and for cancer chemotherapy. In the case of malaria, drug resistance is an ever present and increasing problem throughout the world with parasites developing resistance to all commonly used antimalarial drugs, even those recently introduced such as mefloquine and halofantrin. Multidrug resistance has emerged as a major problem in the treatment of many cancers and remains a major obstacle to the successful control of certain neoplasias with chemotherapy. It is an emerging problem in parasitic protozoa, and a major question to be investigated in this proposal is the similarity of multidrug resistance in parasites to that found in mammalian cells. In the case of malaria, the similarity in the pharmacological features of the chloroquine resistance in P. falciparum, namely the proposed efflux mechanism and the reversal of resistance by verapamil, desipramine and related compounds led to the proposal that a similar mechanism for drug resistance was operating in P. falciparum . We have identified genes that had sequence and predicted structural similarity to the mdr genes and have completed the sequence, analyzed the expressed mRNA and protein. These genes and their encoded proteins are indeed related to the family of genes known as the ATP-Binding Cassette family and have the highest homology with the mdr genes from mouse and human.... Malaria, Plasmodium falciparum, Drug Resistance, Molecular biology, Pharmacology, RA 1.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 11, 1992
- Accession Number
- ADA259217
Entities
People
- Dyann F. Wirth