scholarly journals Increased transport of pteridines compensates for mutations in the high affinity folate transporter and contributes to methotrexate resistance in the protozoan parasite Leishmania tarentolae

1999 ◽  
Vol 18 (9) ◽  
pp. 2342-2351 ◽  
Author(s):  
Christoph Kündig ◽  
Anass Haimeur ◽  
Danielle Légaré ◽  
Barbara Papadopoulou ◽  
Marc Ouellette
Keyword(s):  
Protozoan Parasite ◽  
Leishmania Tarentolae ◽  
High Affinity ◽  
Methotrexate Resistance ◽  
Parasite Leishmania

scholarly journals Amplified DNAs in laboratory stocks of Leishmania tarentolae: extrachromosomal circles structurally and functionally similar to the inverted-H-region amplification of methotrexate-resistant Leishmania major.

1988 ◽  
Vol 8 (12) ◽  
pp. 5188-5199 ◽  
Author(s):  
M L Petrillo-Peixoto ◽  
S M Beverley
Keyword(s):  
Mammalian Cells ◽  
Leishmania Major ◽  
Protozoan Parasite ◽  
Cross Hybridization ◽  
Leishmania Tarentolae ◽  
Pulsed Field ◽  
Methotrexate Resistance ◽  
Pulsed Field Electrophoresis ◽  
Leishmania Spp ◽  
Circular Dnas

We describe the structure of amplified DNA that was discovered in two laboratory stocks of the protozoan parasite Leishmania tarentolae. Restriction mapping and molecular cloning revealed that a region of 42 kilobases was amplified 8- to 30-fold in these lines. Southern blot analyses of digested DNAs or chromosomes separated by pulsed-field electrophoresis showed that the amplified DNA corresponded to the H region, a locus defined originally by its amplification in methotrexate-resistant Leishmania major (S. M. Beverley, J. A. Coderre, D. V. Santi, and R. T. Schimke, Cell 38:431-439, 1984). Similarities between the amplified DNA of the two species included (i) extensive cross-hybridization; (ii) approximate conservation of sequence order; (iii) extrachromosomal localization; (iv) an overall inverted, head-to-head configuration as a circular 140-kilobase tetrameric molecule; (v) two regions of DNA sequence rearrangement, each of which was closely associated with the two centers of the inverted repeats; (vi) association with methotrexate resistance; and (vii) phenotypically conservative amplification, in which the wild-type chromosomal arrangement was retained without apparent modification. Our data showed that amplified DNA mediating drug resistance arose in unselected L. tarentolae, although the pressures leading to apparently spontaneous amplification and maintenance of the H region are not known. The simple structure and limited extent of DNA amplified in these and other Leishmania lines suggests that the study of gene amplification in Leishmania spp. offers an attractive model system for the study of amplification in cultured mammalian cells and tumors. We also introduced a method for measuring the size of large circular DNAs, using gamma-irradiation to introduce limited double-strand breaks followed by sizing of the linear DNAs by pulsed-field electrophoresis.

Amplified DNAs in laboratory stocks of Leishmania tarentolae: extrachromosomal circles structurally and functionally similar to the inverted-H-region amplification of methotrexate-resistant Leishmania major

1988 ◽  
Vol 8 (12) ◽  
pp. 5188-5199
Author(s):  
M L Petrillo-Peixoto ◽  
S M Beverley
Keyword(s):  
Mammalian Cells ◽  
Leishmania Major ◽  
Protozoan Parasite ◽  
Cross Hybridization ◽  
Leishmania Tarentolae ◽  
Pulsed Field ◽  
Methotrexate Resistance ◽  
Pulsed Field Electrophoresis ◽  
Leishmania Spp ◽  
Circular Dnas

We describe the structure of amplified DNA that was discovered in two laboratory stocks of the protozoan parasite Leishmania tarentolae. Restriction mapping and molecular cloning revealed that a region of 42 kilobases was amplified 8- to 30-fold in these lines. Southern blot analyses of digested DNAs or chromosomes separated by pulsed-field electrophoresis showed that the amplified DNA corresponded to the H region, a locus defined originally by its amplification in methotrexate-resistant Leishmania major (S. M. Beverley, J. A. Coderre, D. V. Santi, and R. T. Schimke, Cell 38:431-439, 1984). Similarities between the amplified DNA of the two species included (i) extensive cross-hybridization; (ii) approximate conservation of sequence order; (iii) extrachromosomal localization; (iv) an overall inverted, head-to-head configuration as a circular 140-kilobase tetrameric molecule; (v) two regions of DNA sequence rearrangement, each of which was closely associated with the two centers of the inverted repeats; (vi) association with methotrexate resistance; and (vii) phenotypically conservative amplification, in which the wild-type chromosomal arrangement was retained without apparent modification. Our data showed that amplified DNA mediating drug resistance arose in unselected L. tarentolae, although the pressures leading to apparently spontaneous amplification and maintenance of the H region are not known. The simple structure and limited extent of DNA amplified in these and other Leishmania lines suggests that the study of gene amplification in Leishmania spp. offers an attractive model system for the study of amplification in cultured mammalian cells and tumors. We also introduced a method for measuring the size of large circular DNAs, using gamma-irradiation to introduce limited double-strand breaks followed by sizing of the linear DNAs by pulsed-field electrophoresis.

Natural and synthetic indirubins as potent and selective inhibitors of the protozoan parasite Leishmania donovani

Planta Medica ◽  
2007 ◽  
Vol 73 (09) ◽  
Author(s):  
E Xingi ◽  
D Smirlis ◽  
S Bisti ◽  
V Myrianthopoulos ◽  
P Magiatis ◽  
...  
Keyword(s):  
Leishmania Donovani ◽  
Protozoan Parasite ◽  
Selective Inhibitors ◽  
Parasite Leishmania ◽  
Natural And Synthetic

scholarly journals Genome sequencing of the lizard parasite Leishmania tarentolae reveals loss of genes associated to the intracellular stage of human pathogenic species

2011 ◽  
Vol 40 (3) ◽  
pp. 1131-1147 ◽  
Author(s):  
Frédéric Raymond ◽  
Sébastien Boisvert ◽  
Gaétan Roy ◽  
Jean-François Ritt ◽  
Danielle Légaré ◽  
...  
Keyword(s):  
Genome Sequencing ◽  
Pathogenic Species ◽  
Leishmania Tarentolae ◽  
Parasite Leishmania ◽  
Intracellular Stage

Association of host cell endoplasmic reticulum and mitochondria with the Toxoplasma gondii parasitophorous vacuole membrane: a high affinity interaction

1997 ◽  
Vol 110 (17) ◽  
pp. 2117-2128 ◽  
Author(s):  
A.P. Sinai ◽  
P. Webster ◽  
K.A. Joiner
Keyword(s):  
Endoplasmic Reticulum ◽  
Toxoplasma Gondii ◽  
Host Cell ◽  
Parasitophorous Vacuole ◽  
Protozoan Parasite ◽  
Host Cells ◽  
Parasitophorous Vacuole Membrane ◽  
Vacuole Membrane ◽  
Protein Protein Interaction ◽  
High Affinity

The parasitophorous vacuole membrane (PVM) of the obligate intracellular protozoan parasite Toxoplasma gondii forms tight associations with host mitochondria and the endoplasmic reticulum (ER). We have used a combination of morphometric and biochemical approaches to characterize this unique phenomenon, which we term PVM-organelle association. The PVM is separated from associated mitochondria and ER by a mean distance of 12 and 18 nm, respectively. The establishment of PVM-organelle association is dependent on active parasite entry, but does not require parasite viability for its maintenance. Association is not a consequence of spatial constraints imposed on the growing vacuole. Morphometric analysis indicates that the extent of mitochondrial association with the PVM stays constant as the vacuole enlarges, whereas the extent of ER association decreases. Disruption of host cell microtubules partially blocks the establishment but not the maintenance of PVM-mitochondrial association, and has no significant effect on PVM-ER association. PVM-organelle association is maintained following disruption of infected host cells, as assessed by electron microscopy and by sub-cellular fractionation showing co-migration of fixed PVM and organelle markers. Taken together, the data suggest that a high affinity, potentially protein-protein interaction between parasite and organelle components is responsible for PVM-organelle association.

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