Overcoming innate drug efflux systems to expand anthelmintic vulnerability

About This Grant

Project Summary Nematode parasites are present nearly every place in the world inhabited by humans. Our strategy for controlling these diseases is to use small molecule therapy, however, there has not been a new drug class on the market in 40 years. We propose that endogenous transporter systems of parasites are innate, dynamic, and play a role in the expulsion of drugs from parasites. In this study, we identify the transporter mRNAs expressed in the presence and absence of anthelmintic drugs. We will achieve an understanding of the drugs that bind a nematode transporter using a CRISPR-edited cell line that is optimized for the study of nematode transporters. In addition, we will study the innate transport properties of nematode cells and the inhibition of these transporters with competitive and allosteric inhibitors. Our results will direct future studies aimed at blocking nematode transporters selectively.