The Leishmania donovani histidine acid ecto-phosphatase LdMAcP: insight into its structure and function

Acid ecto-phosphatase activity has been implicated in Leishmania donovani promastigote virulence. Here we report data contributing to the molecular/structural and functional characterization of the Leishmania donovani LdMAcP, member of the histidine acid phosphatase family. LdMAcP, is membrane anchored and shares high sequence identity with the major secreted Leishmania donovani acid phosphatases (LdSAcPs).Sequence comparison of the LdMAcP orthologs in Leishmania spp revealed strain polymorphism and species specificity for the Leishmania donovani complex, responsible for visceral leishmaniasis (Khala azar), proposing thus a potential value of LdMAcP as epidemiological or diagnostic tool. The extracellular orientation of the LdMAcP catalytic domain was confirmed in Leishmania donovani promastigotes, wild type and transgenic overexpressing a recombinant LdMAcP-mRFP1 chimera, as well as in transiently transfected mammalian cells expressing rLdMAcP-His. For the first time it is demonstrated here that LdMAcP confers tartrate resistant acid ecto-phosphatase activity in live Leishmania donovani promastigotes. The latter confirmed the long seeked molecular identity of at least one enzyme contributing to this activity. Interestingly, the Leishmania donovani-rLdMAcP-mRFP1 promastigotes generated in this study, showed significantly higher infectivity and virulence indexes than control parasites in the infection of J774 mouse macrophages highlighting thereby a role for LdMAcP in the para...
Source: BJ Cell - Category: Biochemistry Authors: Tags: BJ Cell Source Type: research