Inhibition of Carbonic Anhydrase Using Aspirin is a Novel Method to Block Schistosomiasis Infection of the Parasitic Trematode,Schistosoma mansoni,in the intermediate snail host,Biomphalaria glabrata

Abstract

Schistosomiasis is a major public health concern worldwide. Although praziquantel is currently available as the only treatment option for schistosomiasis, the absence of reliable diagnostic and prognostic tools highlights the need for the identification and characterization of new drug targets. Recently, we identified theB. glabratahomolog (accession number XP_013075832.1) of human CAXIV, showing 37% amino acid sequence identity, from a BLAST search in NCBI. CA’s are metalloenzymes that catalyze the reversible hydration/dehydration of CO2/HCO3. These enzymes are associated with many physiological processes, and their role in tumorigenesis has been widely implicated. CAs create an acidic extracellular environment that facilitates the survival, metastasis, and growth of cancer cells. In this study, we investigated CA as a potential biomarker for infection inB. glabratasnails. We analysed the expression of theB. glabrataCA encoding transcript in juvenile susceptible and resistant snails, with and without exposure toS. mansoni. Our results showed that the expression of the CA encoding transcript was upregulated during early and prolonged infection susceptible snails (BBO2 and NMRI), but not in the resistant BS-90. Notably, sodium salicylate, a form of aspirin, inhibited the expression of CA, post-exposure, to the parasite. These data show that the expression of CA in the snail-schistosome interaction, represents a novel biomarker for the detection of schistosomes in the snail host. Moreover, this model system may aid in understanding the role of CA in the metastasis and proliferation of cancer cells. Further studies are needed to explore the potential of CA as a biomarker for infection in other schistosomiasis-causing parasites, includingS. japonicumandS. haematobium.