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    Transgenically expressed Parascaris P-glycoprotein-11 can modulate ivermectin susceptibility in Caenorhabditis elegans (2015)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Janssen, I. Jana I. (WE 13)
    Krücken, Jürgen (WE 13)
    Demeler, Janina (WE 13)
    von Samson-Himmelstjerna, Georg (WE 13)
    Forschungsprojekt
    Molekulare und funktionelle Untersuchungen zu P-Glykoprotein assoziierten Mechanismen der Resistenz gegenüber makrozyklischen Laktonen beim Pferdespulwurm Parascaris equorum
    Quelle
    International journal for parasitology. Drugs and drug resistance; 5(2) — S. 44–47
    ISSN: 2211-3207
    Sprache
    Englisch
    Verweise
    URL (Volltext): http://edocs.fu-berlin.de/docs/receive/FUDOCS_document_000000022719
    DOI: 10.1016/j.ijpddr.2015.03.003
    Kontakt
    Institut für Parasitologie und Tropenveterinärmedizin

    Robert-von-Ostertag-Str. 7-13
    Gebäude 35, 22, 23
    14163 Berlin
    Tel.+49 30 838 62310 Fax.+49 30 838 62323
    email:parasitologie@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    P-glycoproteins (Pgps) are suspected to mediate drug extrusion in nematodes contributing to macrocyclic lactone resistance. This association was recently shown for Parascaris Pgp-11. Ivermectin resistance was correlated with the presence of three pgp-11 single nucleotide polymorphisms and/or increased pgp-11 mRNA levels. In the present study, the ability of Pgp-11 to modulate ivermectin susceptibility was investigated by its expression in a pgp-11-deficient Caenorhabditis elegans strain. Expression of Parascaris pgp-11 in two transgenic lines significantly decreased ivermectin susceptibility in a motility (thrashing) assay conducted in liquid medium. The EC50 values increased by 3.2- and 4.6-fold in the two lines relative to a transgenic control strain. This is the first report on the successful functional analysis of a parasitic nematode Pgp in the model organism C. elegans.