Background: Schistosoma mansoni is the etiological agent of schistosomiasis, a debilitating treatment
neglected tropical disease that affects approximately 218 million people worldwide. Despite its importance, the
treatment of schistosomiasis relies on a single drug, praziquantel. Some reports on the resistance of S. mansoni to
this drug have stimulated efforts to develop new drugs to treat this disease. S. mansoni possesses all the same
pyrimidine pathways (de novo, salvage and thymidylate cycles) as those of its host. The opposite scenario is true
for purine metabolism, in which only the salvage pathway is present. These pathways have previously been proposed
as potential drug targets.
Results: Using modern molecular biology techniques, large-scale study of these pathways has become possible;
24 genes have been studied, and several protein structures and kinetic parameters have been determined. Unique
characteristics of schistosomal enzymes have been obtained, which show that this organism possesses two isoforms
of uridine phosphorylase (UP), which share 92% of identity. However, only one isoform has a canonical
function, whereas the second isoform is expressed through all life stages and does not have a known function. In
addition, the methylthioadenosine phosphorylase (MTAP) is one of the enzymes responsible for the previously
described adenosine phosphorylase activity, thus representing one main difference between S. mansoni and its
host. The study of adenine phosphoribosyltransferase has revealed possible differential expression of the APRT
gene in females. This result is consistent with those obtained for the experimental treatment of schistosomiasis in
monkeys with the adenosine analog tubercidin, which eliminates the disease mainly in females.
Conclusion: These important conclusions may aid in the development of new alternative drugs to treat schistosomiasis.