Genetic and molecular basis of drug resistance and species-specific drug action in Schistosome parasites

ABSTRACT: Oxamniquine resistance evolved in the human blood fluke (Schistosoma mansoni) in Brazil in the 1970s. We crossed parental parasites differing ~500-fold in drug response, determined drug sensitivity and marker segregation in clonally-derived F2s, and identified a single QTL (LOD=31) on chromosome 6. A sulfotransferase was identified as the causative gene using RNAi knockdown and biochemical complementation assays and we subsequently demonstrated independent origins of loss-of-function mutations in field-derived and laboratory-selected resistant parasites. These results demonstrate the utility of linkage mapping in a human helminth parasite, while crystallographic analyses of protein-drug interactions illuminate the mode of drug action and provide a framework for rational design of oxamniqui

ORGANISM(S): Schistosoma mansoni

SUBMITTER: Timothy ANDERSON 

PROVIDER: E-GEOD-51847 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress