TRPtracker: a community database for monitoring praziquantel sensitivity at TRPMPZQ variants

Claudia Rohr, Sang-Kyu Park, Kelsilandia Aguiar-Martins, Timothy Anderson, Duncan Berger, Matthew Berriman, Sarah Buddenborg, Amaya Bustinduy, Frédéric Chevalier, James Cotton, Thomas Crellen, Stephen Doyle, Aidan Emery, Julien Kincaid Smith (), Safari Kinung'Hi, Poppy Lamberton, Winka Le Clec’h, Eric Ndombi, Tom Pennance, Candia Rowel, Shannan Summers, John Tushabe, Martin Walker, Bonnie Webster, Joanne Webster, Shona Wilson and Jonathan Marchant ()
Additional contact information
Claudia Rohr: MCW - Medical College of Wisconsin [Milwaukee]
Sang-Kyu Park: MCW - Medical College of Wisconsin [Milwaukee]
Kelsilandia Aguiar-Martins: Department of Pathobiology and Population Sciences - RVC - Royal Veterinary College - University of London [London]
Timothy Anderson: Texas Biomedical Research Institute [San Antonio, TX]
Duncan Berger: The Wellcome Trust Sanger Institute [Cambridge]
Matthew Berriman: University of Glasgow, College of Veterinary Medicine and Life Sciences - University of Glasgow
Sarah Buddenborg: The Wellcome Trust Sanger Institute [Cambridge]
Amaya Bustinduy: LSHTM - London School of Hygiene and Tropical Medicine
Frédéric Chevalier: Texas Biomedical Research Institute [San Antonio, TX]
James Cotton: University of Glasgow, College of Veterinary Medicine and Life Sciences - University of Glasgow
Thomas Crellen: NUS - National University of Singapore, Saw Swee Hock School of Public Health - NUS - National University of Singapore
Stephen Doyle: The Wellcome Trust Sanger Institute [Cambridge]
Aidan Emery: NHM - The Natural History Museum [London]
Julien Kincaid Smith: UMR CBGP - Centre de Biologie pour la Gestion des Populations - Cirad - Centre de Coopération Internationale en Recherche Agronomique pour le Développement - IRD [Occitanie] - Institut de Recherche pour le Développement - INRAE - Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement - Institut Agro Montpellier - Institut Agro - Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement - UM - Université de Montpellier
Safari Kinung'Hi: NIMR - National Institute for Medical Research [Tanzania]
Poppy Lamberton: University of Glasgow, College of Veterinary Medicine and Life Sciences - University of Glasgow
Winka Le Clec’h: Texas Biomedical Research Institute [San Antonio, TX]
Eric Ndombi: KEMRI - Kenya Medical Research Institute, KU - Kenyatta University of Nairobi
Tom Pennance: NHM - The Natural History Museum [London]
Candia Rowel: Ministry of Health Uganda
Shannan Summers: LSHTM - London School of Hygiene and Tropical Medicine
John Tushabe: University of Glasgow
Martin Walker: Department of Pathobiology and Population Sciences - RVC - Royal Veterinary College - University of London [London], DIDE - Department of Infectious Disease Epidemiology [London] - Imperial College London
Bonnie Webster: NHM - The Natural History Museum [London]
Joanne Webster: Department of Pathobiology and Population Sciences - RVC - Royal Veterinary College - University of London [London], DIDE - Department of Infectious Disease Epidemiology [London] - Imperial College London
Shona Wilson: CAM - University of Cambridge [Cambridge, UK]
Jonathan Marchant: MCW - Medical College of Wisconsin [Milwaukee]

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Abstract: Highlights: • A community resource that catalogues natural variation within the ion channel, TRPMPZQ. • Praziquantel sensitivity, and expression levels of TRPMPZQ variants, are assessed in mammalian cells. • Data will aid surveillance of TRPMPZQ variants that may impact clinical PZQ sensitivity. Abstract: The anthelmintic praziquantel (PZQ) has been used for decades as the clinical therapy for schistosomiasis, and remains the only available drug. As a cheap and effective drug therapy for all human disease-causing Schistosoma species, usage of PZQ underpins mass drug administration strategies aimed at eliminating schistosomiasis as a public health problem by 2030. Concern over the potential emergence of resistance to PZQ is therefore warranted, as it would constitute a major threat to this approach. In terms of molecular adaptations conferring PZQ resistance, variation in the sequence and/or expression of the drug target is an obvious mechanism and should be a priority for surveillance efforts. The target of PZQ is a transient receptor potential ion channel, TRPMPZQ, which is established as a locus that regulates schistosome sensitivity to PZQ. Here, we describe the establishment of a community resource, ‘TRPtracker', which coalesces data on TRPMPZQ natural variants together with measurements of individual TRPMPZQ variant sensitivity to PZQ assessed by profiling TRPMPZQ in a heterologous expression system. A compendium of laboratory-generated mutants in TRPMPZQ is also compiled in the TRPtracker database to delimit regions within TRPMPZQ that are critical for PZQ sensitivity. Aggregation of data from multiple research groups into TRPtracker catalogues which TRPMPZQ variants have been functionally profiled, where geographically these variants have been found, their frequency within populations, and their potential impact on PZQ sensitivity. The overall goal is to facilitate rapid community-wide exchange of data to monitor predicted variants of concern that are likely to be associated with decreased PZQ efficacy.

Keywords: Resistance; Transient receptor potential channel; Schistosomiasis; Database (search for similar items in EconPapers)
Date: 2026-04
Note: View the original document on HAL open archive server: https://hal.inrae.fr/hal-05576150v1
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Published in International journal for parasitology. Drugs and drug resistance, 2026, 30, pp.100639. ⟨10.1016/j.ijpddr.2026.100639⟩

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Persistent link: https://EconPapers.repec.org/RePEc:hal:journl:hal-05576150

DOI: 10.1016/j.ijpddr.2026.100639

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