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    Schistosoma mansoni P-glycoprotein levels increase in response to praziquantel exposure and correlate with reduced praziquantel susceptibility

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    messerlietal-revised-final-plusfigs.pdf (250.8Kb)
    Date
    2009-04-28
    Author
    Messerli, Shanta M.  Concept link
    Kasinathan, Ravi S.  Concept link
    Morgan, William  Concept link
    Spranger, Stefani  Concept link
    Greenberg, Robert M.  Concept link
    Metadata
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    Citable URI
    https://hdl.handle.net/1912/2851
    As published
    https://doi.org/10.1016/j.molbiopara.2009.04.007
    Keyword
     Schistosoma mansoni; P-glycoprotein; Multidrug resistance; Praziquantel; ABC transporter 
    Abstract
    One potential physiological target for new antischistosomals is the parasite's system for excretion of wastes and xenobiotics. P-glycoprotein (Pgp), a member of the ATP-binding cassette superfamily of proteins, is an ATP-dependent efflux pump involved in transport of toxins and xenobiotics from cells. In vertebrates, increased expression of Pgp is associated with multidrug resistance in tumor cells. Pgp may also play a role in drug resistance in helminths. In this report, we examine the relationship between praziquantel (PZQ), the current drug of choice against schistosomiasis, and Pgp expression in Schistosoma mansoni. We show that levels of RNA for SMDR2, a Pgp homolog from S. mansoni, increase transiently in adult male worms following exposure to sublethal concentrations (100 - 500 nM) of PZQ. A corresponding, though delayed, increase in anti-Pgp immunoreactive protein expression occurs in adult males following exposure to PZQ. The level of anti-Pgp immunoreactivity in particular regions of adult worms also increases in response to PZQ. Adult worms from an Egyptian S. mansoni isolate with reduced sensitivity to PZQ express increased levels of SMDR2 RNA and anti-Pgp-immunoreactive protein, perhaps indicating a role for multidrug resistance proteins in development or maintenance of PZQ resistance.
    Description
    Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Molecular and Biochemical Parasitology 167 (2009): 54-59, doi:10.1016/j.molbiopara.2009.04.007.
    Collections
    • BioCurrents Research Center
    Suggested Citation
    Preprint: Messerli, Shanta M., Kasinathan, Ravi S., Morgan, William, Spranger, Stefani, Greenberg, Robert M., "Schistosoma mansoni P-glycoprotein levels increase in response to praziquantel exposure and correlate with reduced praziquantel susceptibility", 2009-04-28, https://doi.org/10.1016/j.molbiopara.2009.04.007, https://hdl.handle.net/1912/2851
     

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