Schistosome Na,K-ATPase as a therapeutic target

Na,K-ATPases are ubiquitous membrane-bound enzymes comprising alpha and beta subunits. Here we clone a Na,K-ATPase beta homolog (designated SNaK1 beta) from the human parasitic platyhelminth, Schistosoma mansoni. The predicted protein is about 33 kDa, and contains a single transmembrane domain and multiple conserved motifs. SNaK1 beta and its previously cloned alpha-subunit counterpart (SNaK1 alpha) are both expressed throughout the schistosome life cycle. In adults, both subunits are detected in the tegumental membrane, likely functioning at the host-parasite interface in Na/K exchange. Both SNaK1 genes can be suppressed by RNAi using targetspecific small inhibitory RNAs (siRNAs), and this severely debilitates the parasites both in vitro and in vivo. However, treating schistosomiasis by delivering the siRNAs hydrodynamically to infected mice has no detectable impact on worms. Additionally, treating schistosome-infected mice with the Na,K-ATPase inhibitor, ouabain, is ineffective. Nonetheless, since schistosomes are very susceptible to perturbation in SNaK1 expression, further work to identify other Na,K-ATPase inhibitors as anti-schistosome agents is warranted.