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DNA amplification in arsenite-resistant Leishmania.
S Detke1, K Katakura, K P Chang
1Department of Microbiology and Immunology, Chicago Medical School, Illinois 60064.
Experimental Cell Research
|January 1, 1989
Summary
Leishmania mexicana amazonensis developed arsenite resistance through amplified DNA. This resistance is linked to extrachromosomal circular DNA molecules, suggesting a novel drug resistance mechanism in protozoan parasites.
Area of Science:
- Parasitology
- Molecular Biology
- Genetics
Background:
- Protozoan parasites like Leishmania mexicana amazonensis are significant human pathogens.
- Drug resistance is a major challenge in treating parasitic infections.
- Understanding resistance mechanisms is crucial for developing effective therapies.
Purpose of the Study:
- To investigate the molecular mechanisms of arsenite resistance in Leishmania mexicana amazonensis.
- To identify genetic alterations associated with acquired drug resistance.
Main Methods:
- In vitro selection of arsenite-resistant Leishmania mexicana amazonensis variants.
- Analysis of DNA amplification and extrachromosomal DNA molecules.
- Comparison of resistant variants with wild-type and drug-sensitive revertant strains.
Main Results:
- Arsenite-resistant variants harbored amplified DNA in extrachromosomal supercoiled molecules (~69 kb).
- These circular DNA molecules originated from a single chromosome in wild-type cells.
- Chromosomal changes were observed in resistant cells, and circular molecules were lost in sensitive revertants.
Conclusions:
- Amplification of chromosomal DNA into extrachromosomal circles is a key mechanism of arsenite resistance in Leishmania mexicana amazonensis.
- This finding provides insights into novel drug resistance strategies in protozoan parasites.
- Further research can explore targeting these amplified DNA structures for therapeutic intervention.