Genome Mapping Reveals Drug Resistance Mutation in Peruvian Malaria Parasites

Researchers have used advanced genomic techniques to map the genome of the malaria parasite Plasmodium falciparum in a carefully defined geographical area in Peru and found a mutation that causes the parasite to become resistant to the commonly used drug clindamycin.

Investigators at the Scripps Research Institute (La Jolla, CA, USA) and collaborators from other institutions studied 14 P. falciparum patient isolates taken recently from the Iquitos region of the Peruvian Amazon, an area prone to development of drug resistance, as malaria was eliminated there in the 1960s but reemerged in the 1990s. Samples were analyzed using genome scanning, a microarray-based technique that delineates the majority of single-base changes, indels (mutation class that includes both insertions, deletions, and the combination thereof), and copy number variants distinguishing the coding regions of two clones.

Results published in the September 9, 2010, online edition of the journal Genome Research revealed that the parasite population in the Peruvian Amazon bore only a limited number of genotypes with low recombination frequencies. Despite the essentially clonal nature of some isolates, there were high frequencies of mutations in subtelomeric highly variable genes and internal var genes, indicating mutations arising during self-mating or mitotic replication.

Of particular interest was the identification of a mutation in a noncoding RNA gene that conferred resistance to the antibiotic clindamycin, a lincosamide drug commonly administered in combination with quinine to treat pregnant women and infants for malaria in Peru.

"We were surprised to find that the parasite populations in Peru were much more homogeneous than expected,” said senior author Dr. Elizabeth Winzeler, associate professor of cell biology at the Scripps Research Institute. "The data suggested that the malaria parasites from Iquitos patients were closely related, with some patients harboring parasites that were nearly clones of each other.”

"This was the first-ever demonstrated case of clindamycin resistance,” said Dr. Winzeler. "The data also show parasites could be resistant to related compounds, such as mirincamycin, that are under development. Our findings emphasize the importance of placing new antimalarial compounds in the drug development pipeline, especially compounds with novel mechanisms of actions.”

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