Genome scanning of Amazonian Plasmodium falciparum shows subtelomeric instability and clindamycin-resistant parasites
- Neekesh V. Dharia1,
- David Plouffe2,
- Selina E.R. Bopp1,
- Gonzalo E. González-Páez1,
- Carmen Lucas3,
- Carola Salas3,
- Valeria Soberon3,
- Badry Bursulaya2,
- Tadeusz J. Kochel3,
- David J. Bacon3 and
- Elizabeth A. Winzeler1,2,4
- 1 Department of Cell Biology, ICND 202, The Scripps Research Institute, La Jolla, California 92037, USA;
- 2 Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA;
- 3 Parasitology Program, Naval Medical Research Center Detachment, Lima APO AA 34031-3800, Peru
Abstract
Here, we fully characterize the genomes of 14 Plasmodium falciparum patient isolates taken recently from the Iquitos region using genome scanning, a microarray-based technique that delineates the majority of single-base changes, indels, and copy number variants distinguishing the coding regions of two clones. We show that the parasite population in the Peruvian Amazon bears a limited number of genotypes and low recombination frequencies. Despite the essentially clonal nature of some isolates, we see high frequencies of mutations in subtelomeric highly variable genes and internal var genes, indicating mutations arising during self-mating or mitotic replication. The data also reveal that one or two meioses separate different isolates, showing that P. falciparum clones isolated from different individuals in defined geographical regions could be useful in linkage analyses or quantitative trait locus studies. Through pairwise comparisons of different isolates we discovered point mutations in the apicoplast genome that are close to known mutations that confer clindamycin resistance in other species, but which were hitherto unknown in malaria parasites. Subsequent drug sensitivity testing revealed over 100-fold increase of clindamycin EC50 in strains harboring one of these mutations. This evidence of clindamycin-resistant parasites in the Amazon suggests that a shift should be made in health policy away from quinine + clindamycin therapy for malaria in pregnant women and infants, and that the development of new lincosamide antibiotics for malaria should be reconsidered.
Footnotes
-
↵4 Corresponding author.
E-mail winzeler{at}scripps.edu; fax (858) 784-8926.
-
[Supplemental material is available online at http://www.genome.org. The microarray data from this study have been submitted to the NCBI Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo) under accession no. GSE22861 and are also at http://www.scripps.edu/cb/winzeler/resources/pf_peru.]
-
Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.105163.110.
- Received January 27, 2010.
- Accepted July 29, 2010.