Genetic and molecular basis of drug resistance and species-specific drug action in schistosome parasites (Articolo in rivista)

Type
Label
  • Genetic and molecular basis of drug resistance and species-specific drug action in schistosome parasites (Articolo in rivista) (literal)
Anno
  • 2013-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1126/science.1243106 (literal)
Alternative label
  • Valentim Claudia L.1,2; Cioli Donato3;Chevalier Frédéric D.2; Cao Xiaohang1; Taylor Alexander B.1; Holloway Stephen P.1; Pica-Mattoccia Livia3; Guidi Alessandra 3; Basso Annalisa3; Tsai Isheng J.4; Berriman Matthew4; Carvalho-Queiroz Claudia1; Almeida Marcio2; Aguilar Hector5; Frantz Doug E.5;Hart P. John 1,6; LoVerde Philip T.1; Anderson Timothy J. C.2 (2013)
    Genetic and molecular basis of drug resistance and species-specific drug action in schistosome parasites
    in Science (New York, N.Y.)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Valentim Claudia L.1,2; Cioli Donato3;Chevalier Frédéric D.2; Cao Xiaohang1; Taylor Alexander B.1; Holloway Stephen P.1; Pica-Mattoccia Livia3; Guidi Alessandra 3; Basso Annalisa3; Tsai Isheng J.4; Berriman Matthew4; Carvalho-Queiroz Claudia1; Almeida Marcio2; Aguilar Hector5; Frantz Doug E.5;Hart P. John 1,6; LoVerde Philip T.1; Anderson Timothy J. C.2 (literal)
Pagina inizio
  • 1385 (literal)
Pagina fine
  • 1389 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#altreInformazioni
  • Published Online November 21 2013 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 342 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 6164 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • 1 Departments of Biochemistry and Pathology, University of Texas Health Science Center, San Antonio, TX 78229, USA. 2 Texas Biomedical Research Institute, San Antonio, TX 78245, USA. 3 Institute of Cell Biology and Neurobiology, CNR, Rome, Italy. 4 Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK. 5 Department of Chemistry, The University of Texas at San Antonio, San Antonio, TX 78249, USA. 6 Department of Veterans Affairs, South Texas Veterans Health Care System, San Antonio, TX 78229, USA. (literal)
Titolo
  • Genetic and molecular basis of drug resistance and species-specific drug action in schistosome parasites (literal)
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 second-generation progeny, and identified a single quantitative trait locus (logarithm of odds = 31) on chromosome 6. A sulfotransferase was identified as the causative gene by using RNA interference 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 oxamniquine derivatives that kill both S. mansoni and S. haematobium, the two species responsible for >99% of schistosomiasis cases worldwide. (literal)
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