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

Biochem J. 2015 May 1;467(3):473-86. doi: 10.1042/BJ20141371.


Acid ecto-phosphatase activity has been implicated in Leishmania donovani promastigote virulence. In the present study, we report data contributing to the molecular/structural and functional characterization of the L. donovani LdMAcP (L. donovani membrane acid phosphatase), member of the histidine acid phosphatase (HAcP) family. LdMAcP is membrane-anchored and shares high sequence identity with the major secreted L. donovani acid phosphatases (LdSAcPs). Sequence comparison of the LdMAcP orthologues in Leishmania sp. revealed strain polymorphism and species specificity for the L. donovani complex, responsible for visceral leishmaniasis (Khala azar), proposing thus a potential value of LdMAcP as an epidemiological or diagnostic tool. The extracellular orientation of the LdMAcP catalytic domain was confirmed in L. donovani promastigotes, wild-type (wt) and transgenic overexpressing a recombinant LdMAcP-mRFP1 (monomeric RFP1) chimera, as well as in transiently transfected mammalian cells expressing rLdMAcP-His. For the first time it is demonstrated in the present study that LdMAcP confers tartrate resistant acid ecto-phosphatase activity in live L. donovani promastigotes. The latter confirmed the long sought molecular identity of at least one enzyme contributing to this activity. Interestingly, the L. 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 parasite's virulence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Phosphatase / chemistry*
  • Acid Phosphatase / genetics
  • Acid Phosphatase / metabolism*
  • Animals
  • Cell Line
  • Conserved Sequence
  • Genes, Protozoan
  • HeLa Cells
  • Humans
  • Leishmania / enzymology
  • Leishmania / genetics
  • Leishmania / pathogenicity
  • Leishmania donovani / enzymology*
  • Leishmania donovani / genetics
  • Leishmania donovani / pathogenicity
  • Macrophages / parasitology
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Phylogeny
  • Protozoan Proteins / chemistry*
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Species Specificity
  • Virulence


  • Protozoan Proteins
  • Recombinant Fusion Proteins
  • Acid Phosphatase

Associated data

  • GENBANK/AAC47744
  • GENBANK/AAC79513
  • GENBANK/AAG01046
  • GENBANK/AIF32067
  • PDB/2HPA