Abstract
Recently, we identified and characterized the genes encoding several distinct members of the histidine-acid phosphatase enzyme family from Leishmania donovani, a primitive protozoan pathogen of humans. These included genes encoding the heavily phosphorylated/glycosylated, tartrate-sensitive, secretory acid phosphatases (Ld SAcP-1 and Ld SAcP-2) and the unique, tartrate-resistant, externally-oriented, surface membrane-bound acid phosphatase (Ld MAcP) of this parasite. It had been previously suggested that these enzymes may play essential roles in the growth, development and survival of this organism. In this report, to further examine this hypothesis, we assessed whether members of the L. donovani histidine-acid phosphatase enzyme family were conserved amongst other pathogenic Leishmania and related trypanosomatid parasites. Such phylogenetic conservation would clearly indicate an evolutionary selection for this family of enzymes and strongly suggest and support an important functional role for acid phosphatases to the survival of these parasites. Results of pulsed field gel electrophoresis and Southern blotting showed that homologs of both the Ld SAcPs and Ld MAcP were present in each of the visceral and cutaneous Leishmania species examined (i.e. isolates of L. donovani, L. infantum,L. tropica, L. major and L. mexicana, respectively). Further, results of enzyme assays showed that all of these organisms expressed both tartrate-sensitive and tartrate-resistant acid phosphatase activities. In addition, homologs of both the Ld SAcPs and Ld MAcP genes and their corresponding enzyme activities were also identified in two Crithidia species (C. fasciculata and C. luciliae) and in Leptomonas seymouri. In contrast, Trypanosoma brucei, Trypanosoma cruzi and Phytomonas serpens had only very low levels of such enzyme activities. Cumulatively, results of this study showed that homologs of the Ld SAcPs and Ld MAcP are conserved amongst all pathogenic Leishmania sps. suggesting that they may play significant functional roles in the growth, development and survival of all members of this important group of human pathogens.
Similar content being viewed by others
References
Tropical Disease Research: Progress 1997–98: Fourteenth Programme Report of the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases, World Health Organization, Geneva, Switzerland, 1999
Mottram JC, Brooks DR, Coombs GH: Roles of cysteine proteinases of trypanosomes and Leishmania in host-parasite interactions. Curr Opin Microbiol 1: 455-460, 1998
Ilgoutz SC, McConville MJ: Function and assembly of the Leishmania surface coat. Int J Parasitol 31: 899-908, 2001
Matlashewski G: Leishmania infection and virulence. Med Microbiol Immunol 190: 37-42, 2001
Turco SJ, Spath GF, Beverley SM: Is lipophosphoglycan a virulence factor? A surprising diversity between Leishmania species. Trends Parasitol 17: 223-226, 2001
Bates PA, Dwyer DM: Biosynthesis and secretion of acid phosphatase by Leishmania donovani promastigotes. Mol Biochem Parasitol 26: 289-296, 1987
Bates PA, Hermes I, Dwyer, DM: Leishmania donovani: Immunochemical localization and secretory mechanism of soluble acid phosphatase. Exp Parasitol 68: 335-346, 1989
Doyle PS, Engel JC, Pimenta PFP, Da Silva PP, Dwyer DM: Leishmania donovani: Long-term culture of axenic amastigotes at 37°C. Exp Parasitol 73: 326-334, 1991
Doyle PS, Dwyer, DM: Leishmania: Immunochemical comparison of the secretory (extracellular) acid phosphatases from various species. Exp Parasitol 77: 435-444, 1993
Ellis SL, Shakarian AM, Dwyer DM: Leishmania: Amastigotes synthesize conserved secretory acid phosphatases during human infection. Exp Parasitol 89: 161-168, 1998
Gottlieb M, Dwyer DM: Leishmania donovani: Surface membrane acid phosphatase activity of promastigotes. Exp Parasitol 52: 117-128, 1981
Gottlieb M, Dwyer DM: Protozoan parasite of humans: Surface membrane with externally disposed acid phosphatase. Science 212: 939-940, 1981
Gottlieb M, Dwyer DM: Identification and partial characterization of an extracellular acid phosphatase activity of Leishmania donovani promastigotes. Mol Cellular Biol 2: 76-81, 1982
Lovelace JK, Dwyer DM, Gottlieb M: Purification and characterization of the extracellular acid phosphatase of Leishmania donovani. Mol Biochem Parasitol 20: 234-251, 1986
Das S, Saha AK, Ramaley AT, Glew RH, Dowling JN, Kajiyoshi M, Gottlieb M: Hydrolysis of phosphoproteins and inositol phosphates by cell surface phosphatase of Leishmania donovani. Mol Biochem Parasitol 20: 143-153, 1986
Ramaley AT, Das S, Campbell PI, La Rocca GM, Pope MT, Glew RH: Characterization of Leishmania donovani acid phosphatases. J Biol Chem 260: 880-886, 1985
Shakarian AM, Ellis SL, Mallinson DJ, Olafson RW, Dwyer DM: Two tandemly arrayed genes encode the (histidine) secretory acid phosphatases of Leishmania donovani. Gene 196: 127-137, 1997
Shakarian AM, Joshi MB, Ghedin E, Dwyer DM: Molecular dissection of the functional domains of a unique, tartrate-resistant, surface membrane acid phosphatase in the primitive human pathogen Leishmania donovani. J Biol Chem 277: 17994-18001, 2002
Bangs JD, Uyetake L, Brickman MJ, Balber AE, Boothroyd JC: Molecular cloning and cellular localization of a BiPhomologue in Trypanosoma brucei. Divergent ER retention signals in a lower eukaryote. J Cell Sci 105: 1101-1113, 1993
Miles, MA, Toye PJ, Oswald SC, Godfrey DG: The identification by isoenzyme patterns of two distinct strain-groups of Trypanosoma cruzi, circulating independently in a rural area of Brazil. Trans R Soc Trop Med Hyg 71: 217-225, 1977
Serrano MG, Nunes LR, Campaner M, Buck GA, Camargo EP, Teixeira MM: Trypanosomatidae: Phytomonas detection in plants and phytophagous insects by PCR amplification of a genus-specific sequence of the spliced leader gene. Exp Parasitol 91: 268-279, 1999
Bates PA, Hermes I, Dwyer DM: Golgi-mediated post-translational processing of secretory acid phosphatase by Leishmania donovani promastigotes. Mol Biochem Parasitol 39: 247-256, 1990
Debrabant A, Bastien P, Dwyer DM: A unique surface membrane anchored purine-salvage enzyme is conserved among a group of primitive eukaryotic human pathogens. Mol Cellular Biochem 220: 109-116, 2001
Cruz AK, Titus R, Beverley SM: Plasticity in chromosome number and testing of essential genes in Leishmania by targeting. Proc Natl Acad Sci USA 90: 1599-1603, 1993
Kebede A, DeDoncker S, Arevalo J, LeRay D, Dujardin, JC: Size-polymorphism of mini-exon gene-bearing chromosomes among natural populations of Leishmania, sub genus Viannia. Int J Parasitol 29: 549-557, 1999
Shakarian AM, Dwyer DM: Structurally conserved soluble acid phosphatases are synthesized and released by Leishmania major promastigotes. Exp Parasitol 95: 79-84, 2000
Coombs GH, Hassan HF, Lockwood BC, Mallinson DJ, North MJ, Alunda JM, Tetley L: Phosphomonoesterases and proteinases of Leishmanias, In: K.-P. Chang, D. Snary (eds). Host-Parasite Cellular and Molecular Interactions in Protozoal Infections, (NATO ASI Series H, vol. 11). Springer-Verlag, Berlin, 1987, pp 189-195
Wiese M, Ilg T, Lottspeich F, Overath P: Ser/Thr-rich repetitive motifs as targets for phosphoglycan modification in Leishmania mexicana secreted acid phosphatase. EMBO J 14: 1067-1074, 1995
Wiese M, Berger O, Stierhof Y-D, Wolfram M, Fuchs M, Overath P: Gene cloning and cellular localization of a membrane-bound acid phosphatase of Leishmania mexicana. Mol Biochem Parasitol 82, 153-165, 1996
Hassan HF, Coombs GH: Phosphomonoesterases of Leishmania mexicana mexicana and other flagellates. Mol Biochem Parasitol 23: 285-296, 1987
Gottlieb M: Enzyme regulation in a trypanosomatid: effect of purine starvation on levels of 3′-nucleotidase activity. Science 227: 72-74, 1985
Hunt RC, Ellar DJ: Isolation of the plasma membrane of a trypanosomatid flagellate: General characterization and lipid composition. Biochim Biophys Acta 339: 173-189, 1974
Lettelier ME, Repetto Y, Aldunate J, Morello A: Acid and alkaline phosphatase activity in Trypanosoma cruzi epimastigotes. Comp Biochem Physiol 81: 47-51, 1985
Schell D, Stierhof Y-D, Overath P: Purification and characterization of a tartrate-sensitive acid phosphatase of Trypanosoma brucei. FEBS Lett 271: 67-70, 1990
Bakalara N, Santarelli X, Davis C, Baltz T: Purification, cloning and characterization of an acidic ectoprotein phosphatase differentially expressed in the infectious bloodstream from of Trypanosoma brucei. J Biol Chem 275: 8863-8871, 2000
Fernandes AP, Nelson K, Beverley SM: Evolution of nuclear ribosomal RNAs in kinetoplastid protozoa: Perspectives on the age and origins of parasitism. Proc Natl Acad Sci USA 90: 11608-11612, 1993
Mallinson DJ, Hassan HF, Tetley L, Coombs GH: Acid phosphatase activities of Leishmania major promastigotes. Med Sci Res 16: 521-522, 1988
Eeckhout Y: Studies on acid hydrolases and on catalase of the try-panosomatid Crithidia luciliae. In: H. van den Bossche (ed). Comparative Biochemistry of Parasites. Academic Press, New York, 1972, pp 297-315
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Shakarian, A.M., Joshi, M.B., Yamage, M. et al. Members of a unique histidine acid phosphatase family are conserved amongst a group of primitive eukaryotic human pathogens. Mol Cell Biochem 245, 31–41 (2003). https://doi.org/10.1023/A:1022851914014
Issue Date:
DOI: https://doi.org/10.1023/A:1022851914014