Species-specific antimonial sensitivity in Leishmania is driven by post-transcriptional regulation of XXXX .

@entity1 @entity15669 @entity234 @entity232 @entity4536 @entity3261
Leishmania is a digenetic protozoan parasite causing @entity232 in @entity1 . The different clinical forms of @entity232 are caused by more than twenty species of Leishmania that are transmitted by nearly thirty species of phlebotomine sand flies. Pentavalent antimonials (such as Pentostam or Glucantime) are the first line drugs for treating @entity232 . Recent studies suggest that pentavalent antimony (Sb(V)) acts as a pro-drug, which is converted to the more active trivalent form (Sb(III)). However, sensitivity to trivalent antimony varies among different @entity15669 . In general, @entity15669 causing @entity4536 ( @entity4536 ) are more sensitive to Sb(III) than the species responsible for @entity234 ( @entity234 ). Leishmania aquaglyceroporin ( @entity3261 ) facilitates the adventitious passage of antimonite down a concentration gradient. In this study, we show that @entity15669 causing @entity4536 accumulate more antimonite, and therefore exhibit higher sensitivity to antimonials, than the species responsible for @entity234 . This species-specific differential sensitivity to antimonite is directly proportional to the expression levels of @entity3261 mRNA. We show that the stability of @entity3261 mRNA in different @entity15669 is regulated by their respective 3'-untranslated regions. The differential regulation of @entity3261 mRNA explains the distinct antimonial sensitivity of each species.
