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

Author:

Parn Simone,Lewis Gabriela,Knight MattyORCID

Abstract

ABSTRACTSchistosomiasis 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 (National Center for Biotechnology Information). Carbonic Anhydrases (CAs) 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 the role of CA inhibition inB. glabratasnails exposed toS. mansonimiracidia. We analyzed 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 mRNA encoding transcript was upregulated during early and prolonged infection in susceptible snails (BBO2), but not in the resistant BS-90 stock. Notably, sodium salicylate, a form of aspirin, inhibited the expression of CA, post-exposure, to the parasite. Increasing research between parasites and cancer has shown that schistosomes and cancer cells share similarities in their capacity to proliferate, survive, and evade host immune mechanisms. Here, we show that this model system is a potential new avenue for 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.

Publisher

Cold Spring Harbor Laboratory

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