Characterization of phosphate transporter(s) and understanding their role in Leishmania donovani parasite
Inorganic phosphate (Pi) is shown to be involved in excretion of methylglyoxal (MG) in the promastigote form of Leishmania donovani parasite. Absence of Pi leads to its accumulation inside the parasite. Accumulation of MG is toxic to the parasite and utilizes glyoxylase as well as excretory pathways for its detoxification. In addition, Pi is also reported to regulate activities of ectoenzymes and energy metabolism (glucose to pyruvate) etc. Thus, it is known to cumulatively affect the growth of Leishmania parasite. Hence the transporters, which allow the movement of Pi across the membrane, can prove to be a crucial drug target. Therefore, we characterized two phosphate transporters in Leishmania (i) H+ dependent myo-inositol transporter (LdPHO84), and (ii) Na+ dependent transporter (LdPHO89), based on similar studies done previously on other lower organisms and trypanosomatids. We tried to understand the secondary structure of these two proteins and confirm modulation in their expression with the change in Pi concentration outside. Moreover, their modes of action were also measured in the presence of specific inhibitors (LiF, CCCP). Further analysis on the physiological role of these transporters in various stages of the parasite life cycle needs to be entrenched.
KeywordsLeishmania inorganic phosphate Pi transporters methylglyoxal drug resistance
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- Desjeux P. 2004. Leishmaniasis: current situation and new perspectives. Comparative Immunology, Microbiology & Infectious Diseases, 27, 305–318. DOI: 10.1016/j.cimid.2004.03.004Google Scholar
- Dick C.F., Dos-Santos A.L., Fonseca-de-Souza A.L., Rocha-Ferreira J., Meyer-Fernandes J.R. 2010. Trypanosoma rangeli: differential expression of ecto-phosphatase activities in response to inorganic phosphate starvation. Experimental Parasitology, 124, 386–393. DOI: 10.1016/j.exppara.2009.12.006CrossRefGoogle Scholar
- Dick C.F., Dos-Santos A.L., Majerowicz D., Gondim K.C., Caruso-Neves C., Silva I.V., et al. 2012. Na+-dependent and Na+-independent mechanisms for inorganic phosphate uptake in Trypanosoma rangeli. Biochimica et Biophysica Acta, 1820, 1001–1008. DOI: 10.1016/j.bbagen.2012.02.019CrossRefGoogle Scholar
- Lom J. 1976. Biology of the trypanosomes and trypanoplasms of fish. In: (Eds W. H. R. Lumsden, and D. A. Evans) Biology of the Kinetoplastida. Academic Press, London/New York/San Francisco. 269–337Google Scholar
- Margarane M., UniProt Consorsium. 2011. UniProt Knowledgebase: a hub of integrated protein data. Database (Oxford), 2011, bar009. DOI: 10.1093/database/bar009Google Scholar
- Russo-Abrahao T., Alves-Bezerra M., Majerowicz D., Freitas-Mesquita A. L., Dick C. F., Gondim K. C., Meyer-Fernandes J. R. 2013. Transport of inorganic phosphate in Leishmania infantum and compensatory regulation at low inorganic phosphate concentration. Biochimica et Biophysica Acta, 1830, 2683–2689CrossRefGoogle Scholar
- Russo-Abrahao T., Koeller C.M., Steinmann M.E., Silva-Rito S., Marins-Lucena T., Alves-Bezerra M., et al. 2017. H+ dependent inorganic phosphate uptake in Trypanosoma brucei is influenced by myo-inositol transporter. Journal of Bioenergetics and Biomembranes, 49, 183–194. DOI: 10.1007/s10863-017-9695-yCrossRefGoogle Scholar
- Samira A., Philippe L. 2017. In vitro effects of purine and pyrimidine analogues on Leishmania donovani and Leishmania infantum promastigotes and intracellular amastigotes. Acta Parasitologica, 62, 582–588. DOI: 10.1515/ap-2017-0070Google Scholar
- Tyler P., Sudhandiran G., Hobbs S. B., Seyfang A. 2004. Substrate specificity of the Leishmania donovani myo-inositol transporter: critical role of inositol C-2, C-3 and C-5 hydroxyl groups. Molecular & Biochemical Parasitology 135, 133–141. DOI: 10.1016/j.molbiopara.2004.01.015CrossRefGoogle Scholar
- Vieira D. P., Paletta-Silva R., Saraiva E. M., Lopes A. H., Meyer-Fernandes J. R. 2011. Leishmania chagasi: an ecto-3’-nucleotidase activity modulated by inorganic phosphate and its possible involvement in parasite-macrophage interaction. Experimental Parasitology, 127, 702–707. DOI: 10.1016 /j.exppara.2010.11.003CrossRefGoogle Scholar
- WHO 2015. Kala-Azar elimination programme: report of a WHO consultation of partners, Geneva, Switzerland, 10–11 February 2015Google Scholar