Proline transport in Leishmania donovani amastigotes: dependence on pH gradients and membrane potential

Glaser, Theresa A.; Mukkada, Antony J.

doi:10.1016/0166-6851(92)90194-o

Cited by 41 publications

(33 citation statements)

References 22 publications

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“…Life sustenance in such a condition becomes much more challenging since Leishmania utilizes the proton motive force for H + -driven glucose and amino acid uptake (Zilberstein and Dwyer, 1985;Bonay and Cohén, 1983;Glaser and Mukkada, 1992). Therefore, the parasite must possess robust acid extrusion machinery to resist a drop in intracellular pH resulting from rapid influx of protons and also from generation of metabolic acids.…”

Section: Discussionmentioning

confidence: 99%

Interplay between a cytosolic and a cell surface carbonic anhydrase in pH homeostasis and acid tolerance of Leishmania

Pal

Abbasi

Mondal

et al. 2017

Journal of Cell Science

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Leishmania parasites have evolved to endure the acidic phagolysosomal environment within host macrophages. How Leishmania cells maintain near-neutral intracellular pH and proliferate in such a proton-rich mileu remains poorly understood. We report here that, in order to thrive in acidic conditions, Leishmania major relies on a cytosolic and a cell surface carbonic anhydrase, LmCA1 and LmCA2, respectively. Upon exposure to acidic medium, the intracellular pH of the LmCA1 +/− , LmCA2 +/− and LmCA1 +/− :LmCA2 +/− mutant strains dropped by varying extents that led to cell cycle delay, growth retardation and morphological abnormalities. Intracellular acidosis and growth defects of the mutant strains could be reverted by genetic complementation or supplementation with bicarbonate. When J774A.1 macrophages were infected with the mutant strains, they exhibited much lower intracellular parasite burdens than their wild-type counterparts. However, these differences in intracellular parasite burden between the wild-type and mutant strains were abrogated if, before infection, the macrophages were treated with chloroquine to alkalize their phagolysosomes. Taken together, our results demonstrate that haploinsufficiency of LmCA1 and/or LmCA2 renders the parasite acid-susceptible, thereby unravelling a carbonic anhydrase-mediated pH homeostatic circuit in Leishmania cells.

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Section: Discussionmentioning

confidence: 99%

Interplay between a cytosolic and a cell surface carbonic anhydrase in pH homeostasis and acid tolerance of Leishmania

Pal

Abbasi

Mondal

et al. 2017

Journal of Cell Science

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“…In comparison, the promastigote-to-amastigote cytodifferentiation is a profound morphological and physiological transformation. During differentiation, the parasite loses its flagellum, rounds up, changes its glycoconjugate coat (13, 21,22,39), and starts to express a set of metabolic enzymes optimally active at low pHs (14,25). The survival of the parasite inside the macrophage phagolysosome is associated with its ability to down-regulate many effector and accessory functions of its host cell, including oxygen metabolite-mediated killing and the capacity of the macrophage to act as an efficient antigen-presenting cell (5,20).…”

mentioning

confidence: 99%

“…In comparison, the promastigote-to-amastigote cytodifferentiation is a profound morphological and physiological transformation. During differentiation, the parasite loses its flagellum, rounds up, changes its glycoconjugate coat (13,21,22,39), and starts to express a set of metabolic enzymes optimally active at low pHs (14,25 functions of its host cell, including oxygen metabolite-mediated killing and the capacity of the macrophage to act as an efficient antigen-presenting cell (5, 20). Glycoconjugates that coat the promastigote have been shown to play a critical role in the mechanism of entry of the parasite into its host cell and in the modulation of the host immune response (reviewed in references 24 and 38).…”

mentioning

confidence: 99%

Developmental gene expression in Leishmania donovani: differential cloning and analysis of an amastigote-stage-specific gene.

Charest¹,

1994

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Leishmania protozoans are the causative agents of human leishmaniasis, which includes a spectrum of diseases ranging from self-healing skin ulcers to fatal visceral infections. Leishmania donovani causes visceral leishmaniasis, also known as kala-azar, which has a high mortality rate if not treated. The Leishmania protozoans exist as extracellular flagellated promastigotes in the alimentary tract of the sand fly and are transmitted to the mammalian hosts through the bite of the insect. Once injected through the skin, the promastigotes are taken up by macrophages, rapidly differentiate into amastigotes, and start to multiply within the phagolysosomal compartment. As the infected cells rupture, amastigotes subsequently infect other macrophages, giving rise to the various symptoms associated with leishmaniasis (23).While in the midgut of the insect, newly transformed promastigotes, functionally avirulent, progressively acquire capacity for infection and migrate to the mouthparts (30, 32). This process, termed metacyclogenesis, is concurrent with the differential expression of major surface glycoconjugates which mediate the migration of promastigotes in the alimentary tract and prepare the organism for the serum environment (27,28,31,33). In comparison, the promastigote-to-amastigote cytodifferentiation is a profound morphological and physiological transformation. During differentiation, the parasite loses its flagellum, rounds up, changes its glycoconjugate coat (13,21,22,39), and starts to express a set of metabolic enzymes optimally active at low pHs (14,25 functions of its host cell, including oxygen metabolite-mediated killing and the capacity of the macrophage to act as an efficient antigen-presenting cell (5, 20). Glycoconjugates that coat the promastigote have been shown to play a critical role in the mechanism of entry of the parasite into its host cell and in the modulation of the host immune response (reviewed in references 24 and 38).Because of difficulties in obtaining a sufficient number of pure and viable amastigotes, the biology of this form of the parasite has not been well characterized. The importance of the promastigote-amastigote cytodifferentiation for the establishment of infection in the mammalian host has prompted us to identify molecular events involved in this process. Our approach was to identify Leishmania genes developmentally expressed during the amastigote stage. Our assumption was that genes expressed only by amastigotes were likely to be essential for the survival of the parasite in its human host.In this study, we have characterized an amastigote-stagespecific gene (A2 gene) and determined the physiological conditions required to induce its expression. We also demonstrate that the A2 gene product is recognized by serum from a kala-azar patient and has identity with a major antigen developmentally expressed by the pathologic forms of the malariaassociated protozoan Plasmodium falciparum. These results suggest that the Leishmania and Plasmodium parasites, phylogenetically distant par...

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“…Very hyperpolarized Vm values are found (-113 mV; Vieira et al, 1995;Marchesini & Docampo, 2002) after bisoxonol distribution in promastigotes, and less hyperpolarized Vm are found in amastigotes (-75 mV; Marchesini & Docampo, 2002). The activity of DCCD on the electrochemical gradient created by H + pumps coupled to DIDS sensitive anion transporters have been implicated in the promastigote Vm (Vieira et al, 1995;Marchesini & Docampo 2002) and Vieira et al, (1995), concluded that there is no contribution from K + or Na + to the Leishmania Vm, despite previous data where distribution of tetraphenylphosphonium bromide points to K + (Glaser et al, 1992) as in other eukaryotes. Again the presumed DCCD-sensitive H + pump activity was shown in intracellular compartments of Leishmania promastigotes, but the proposed model couples its function to DIDS sensitive transporters on the parasite plasma membrane.…”

Section: Leishmania Plasma Membranementioning

confidence: 47%

“…Molecules involved in nutrient uptake are found in Trypanosomatidae (Glaser & Mukkada, 1992;ter Kulle, 1993;Vieira et al, 1996;Tetaud et al, 1994). Transport of D-glucose and Dproline is mediated by H + symporters in Leishmania (Zilberstein & Dwyer, 1985;Zilberstein, 1993).…”

Section: Leishmania Plasma Membranementioning

confidence: 99%

Electrical Membrane Properties in the Model Leishmania-Macrophage

Camacho¹

2012

Patch Clamp Technique

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Proline transport in Leishmania donovani amastigotes: dependence on pH gradients and membrane potential

Cited by 41 publications

References 22 publications

Interplay between a cytosolic and a cell surface carbonic anhydrase in pH homeostasis and acid tolerance of Leishmania

Interplay between a cytosolic and a cell surface carbonic anhydrase in pH homeostasis and acid tolerance of Leishmania

Developmental gene expression in Leishmania donovani: differential cloning and analysis of an amastigote-stage-specific gene.

Electrical Membrane Properties in the Model Leishmania-Macrophage

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