NEW YORK (GenomeWeb) – The National Institutes of Health has awarded a team of Texas Biomedical Research Institute investigators a five-year, $3.5 million grant to investigate the genetics underlying drug resistance in the parasitic flatworm schistosoma.
The schistosomes live in certain types of freshwater snails, and humans can become infected if they come in contact with contaminated water. Praziquantel (PZQ) is primarily used to treat infection, but the drug is only effective against adult parasites and its exact mechanism of action is unknown. As a result, there is a concern that wide-spread resistance may develop.
"We currently don't know how the drug works and what the mechanism of action is," Texas Biomed research and the project's principle investigator Tim Anderson said in a statement. "Once we know how the drug works, we can start to improve it. One way to understand how the drug works is to identify the genes that make parasites resistant."
With the NIH funding, Anderson and his colleagues also hope to develop molecular markers for field surveillance of resistance in treatment programs.
In a previous study, the researchers created genetic crosses between sensitive and resistant parasites, and identified a region in the schistosoma genome linked to PZQ resistance. They plan to now focus in on the genes and mutations conferring resistance in these crosses, and see if they are the same that are involved in drug resistance in infected patients in Kenya and Uganda.
"We can obtain parasite eggs from fecal samples collected from patients, hatch parasite larvae, and sequence their genomes," Anderson added. "We can then examine the same patients after PZQ treatment. A proportion of these patients will still be infected: we can identify the genes involved in resistance by sequencing the parasites that survive drug treatment."