Genome-scanning of Amazonian Plasmodium falciparum shows subtelomeric instability and clindamycin resistant parasites

ABSTRACT: Here we fully characterize the genomes of 14 Plasmodium falciparum patient isolates taken recently from the Iquitos regions using genome-scanning, a microarray-based technique which 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 is highly structured with 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 1 or 2 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 pair-wise 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 clindamycin EC50 in strains harboring one of these mutations. This evidence of clindamycin resistant parasites in the Amazon suggests 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. Genome DNA from Peruvian Isolates vs. Reference 3D7

ORGANISM(S): Plasmodium falciparum

SUBMITTER: Neekesh Dharia 

PROVIDER: E-GEOD-22861 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress