Decades-old mystery solved: Two independent research groups find answer

These findings lay the foundation for diagnostic tests to help identify specific patients and regions with drug-resistant parasites, as well as to develop treatments that can overcome this challenge

"We have two separate papers that came to the exact same conclusion using completely different methods," said Texas Biomedical Professor Dr.

Schistosomiasis is a parasitic disease caused by tiny flatworms called schistosomiasis

"We have a drug that treats a huge number of parasites, and it works, but it's not perfect," said Dr.

The drug binds to a special type of channel on the cell membrane called a transient receptor potential (TRP) channel

Anderson's team spent five years identifying this channel as the primary way the drug interacts with the worm

Specifically, they identified hundreds of worms that showed resistance to the drug, as well as those that were susceptible and died

By taking this approach, they were able to more accurately quantify how resistant the worms were that survived: "They were more than 377 times more resistant than the dead worms," ​​said Dr.

To find the genetic drivers behind this resistance, they conducted a genome-wide association study to find out whether there were large differences between the two groups in any part of the roundworm's genetic code

"It's not an ordinary TRP channel, but the exact same TRP channel that our collaborator Jonathan Marchant discovered using a completely different approach," Le Clec'h said

Dr.

"Our work identified a specific mutation in the TRP channel that may lead to loss of praziquantel sensitivity

The two labs had been working independently until they learned of each other's investigations at a molecular parasitology meeting in 2017

Much work remains to be done to fully understand drug resistance in schistosomiasis

"This really sets the stage for a large-scale screening of natural schistosome populations to see if we have a resistance problem," said Anderson,

The work involved an international collaboration with researchers from five countries on three continents

Journal Reference :

1. Winka Le Clec’h, Frédéric D.
   Chevalier, Ana Carolina A.
   Mattos, Amanda Strickland, Robbie Diaz, Marina McDew-White, Claudia M.
   Rohr, Safari Kinung’hi, Fiona Allan, Bonnie L.
   Webster, Joanne P.
   Webster, Aidan M.
   Emery, David Rollinson, Amadou Garba Djirmay, Khalid M.
   Al Mashikhi, Salem Al Yafae, Mohamed A.
   Idris, Hélène Moné, Gabriel Mouahid, Philip LoVerde, Jonathan S.
   Marchant , Timothy JC Anderson.
   Genetic analysis of praziquantel response in schistosome parasites implicates a transient receptor potential channel .
   Science Translational Medicine , 2021; 13 (625) DOI: 10.
   1126/scitranslmed.
   abj9114 ary 6, 2022).