What's new for 'Trypanosomatids' in PubMed

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Sent on Tuesday, 2010 Dec 21
Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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PubMed Results

Items 1 - 8 of 8

1.	Amino Acids. 2010 Dec 18. [Epub ahead of print] Lysine transporters in human trypanosomatid pathogens. Inbar E, Canepa GE, Carrillo C, Glaser F, Suter Grotemeyer M, Rentsch D, Zilberstein D, Pereira CA. Faculty of Biology, Technion-Israel Institute of Technology, 32000, Haifa, Israel. Abstract In previous studies we characterized arginine transporter genes from Trypanosoma cruzi and Leishmania donovani, the etiological agents of chagas disease and kala azar, respectively, both fatal diseases in humans. Unlike arginine transporters in higher eukaryotes that transport also lysine, these parasite transporters translocate only arginine. This phenomenon prompted us to identify and characterize parasite lysine transporters. Here we demonstrate that LdAAP7 and TcAAP7 encode lysine-specific permeases in L. donovani and T. cruzi, respectively. These two lysine permeases are both members of the large amino acid/auxin permease family and share certain biochemical properties, such as specificity and Km. However, we evidence that LdAAP7 and TcAAP7 differ in their regulation and localization, such differences are likely a reflection of the dissimilar L. donovani and T. cruzi life cycles. Failed attempts to delete both alleles of LdAAP7 support the premise that this is an essential gene that encodes the only lysine permeases expressed in L. donovani promastigotes and T. cruzi epimastigotes, respectively.
	PMID: 21170560 [PubMed - as supplied by publisher]
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2.	FASEB J. 2010 Dec 17. [Epub ahead of print] A constitutive pan-hexose permease for the Plasmodium life cycle and transgenic models for screening of antimalarial sugar analogs. Blume M, Hliscs M, Rodriguez-Contreras D, Sanchez M, Landfear S, Lucius R, Matuschewski K, Gupta N. *Department of Molecular Parasitology, Humboldt University, Berlin, Germany; Abstract Glucose is considered essential for erythrocytic stages of the malaria parasite, Plasmodium falciparum. Importance of sugar and its permease for hepatic and sexual stages of Plasmodium, however, remains elusive. Moreover, increasing global resistance to current antimalarials necessitates the search for novel drugs. Here, we reveal that hexose transporter 1 (HT1) of Plasmodium berghei can transport glucose (K(m)f87 μ M), mannose (K(i)f93 μ M), fructose (K(i)f0.54 mM), and galactose (K(i)f5 mM) in Leishmania mexicana mutant and Xenopus laevis; and, therefore, is functionally equivalent to HT1 of P. falciparum (Glc, K(m)f175 μ M; Man, K(i)f276 μ M; Fru, K(i)f1.25 mM; Gal, K(i)f5.86mM). Notably, a glucose analog, C3361, attenuated hepatic (IC(50)f15 μ M) and ookinete development of P. berghei. The PbHT1 could be ablated during intraerythrocytic stages only by concurrent complementation with PbHT1-HA or PfHT1. Together; these results signify that PbHT1 and glucose are required for the entire life cycle of P. berghei. Accordingly, PbHT1 is expressed in the plasma membrane during all parasite stages. To permit a high-throughput screening of PfHT1 inhibitors and their subsequent in vivo assessment, we have generated Saccharomyces cerevisiae mutant expressing codon-optimized PfHT1, and a PfHT1-dependent Δpbht1 parasite strain. This work provides a platform to facilitate the development of drugs against malaria, and it suggests a disease-control aspect by reducing parasite transmission.-Blume, M., Hliscs, M., Rodriguez-Contreras, D., Sanchez, M., Landfear, S., Lucius, R., Matuschewski, K., Gupta, N. A constitutive pan-hexose permease for the Plasmodium life cycle and transgenic models for screening of antimalarial sugar analogs.
	PMID: 21169382 [PubMed - as supplied by publisher]
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3.	Arch Biochem Biophys. 2010 Dec 15. [Epub ahead of print] Tryparedoxin peroxidases from Trypanosoma cruzi: high efficiency in the catalytic elimination of hydrogen peroxide and peroxynitrite. Piñeyro MD, Arcari T, Robello C, Radi R, Trujillo M. Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay; Unidad de Biología Molecular-Institut Pasteur Montevideo, Montevideo, Uruguay. Abstract During host cell infection, Trypanosoma cruzi parasites are exposed to reactive oxygen and nitrogen species. As part of their antioxidant defense systems, they express two tryparedoxin peroxidases (TXNPx), thiol-dependent peroxidases members of the peroxiredoxin family. In this work, we report a kinetic characterization of cytosolic (c-TXNPx) and mitochondrial (m-TXNPx) tryparedoxin peroxidases from Trypanosoma cruzi. Both c-TXNPx and m-TXNPx rapidly reduced hydrogen peroxide (k = 3.0 x 10(7) and 6 x 10(6) M(-1) s(-1) at pH 7.4 and 25°C, respectively) and peroxynitrite (k = 1.0 x 10(6) and k = 1.8 x 10(7) M(-1) s(-1) at pH 7.4 and 25°C, respectively). The reductive part of the catalytic cycle was also studied, and the rate constant for the reduction of c-TXNPx by T. brucei tryparedoxin I was 1.3 x 10(6) M(-1) s(-1). The catalytic role of two conserved cysteine residues in both TXNPxs was confirmed with the identification of Cys52 and Cys173 (in c-TXNPX) and Cys81 and Cys204 (in m-TXNPx) as the peroxidatic and resolving cysteines, respectively. Our results indicate that mitochondrial and cytosolic TXNPxs from Trypanosoma cruzi are highly efficient peroxidases that reduce hydrogen peroxide and peroxynitrite, and contribute to the understanding of their role as virulence factors reported in vivo. Copyright © 2010. Published by Elsevier Inc.
	PMID: 21167808 [PubMed - as supplied by publisher]
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4.	J Am Acad Dermatol. 2011 Jan;64(1):202-3. Nitazoxanide in the treatment of chronic cutaneous leishmaniasis resistant to traditional sodium stibogluconate. Gurgen J, Hogan D, Grace E, Johnson D. Suncoast Hospital, affiliated with Nova Southeastern University, Fort Lauderdale, Florida.
	PMID: 21167419 [PubMed - in process]
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5.	Mol Biochem Parasitol. 2010 Dec 14. [Epub ahead of print] Artificial linear episome-based protein expression system for protozoon Leishmania tarentolae. Kushnir S, Cirstea I, Basiliya L, Lupilova N, Breitling R, Alexandrov K. Department of Chemical Biology Max-Planck-Institute for Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany. Abstract The trypanosomatid protozoon Leishmania tarentolae is a well-established model organism for studying causative agents of several tropical diseases that was more recently developed as a host for recombinant protein production. Although several expression architectures based on foreign RNA polymerases have been established for this organism, all of them rely on integration of the expression cassette into the genome. Here, we exploit a new type of expression architecture based on linear elements. These expression vectors were propagated in E. coli as circular plasmids and converted into linear episomes with telomere-like structures prior to transfection of L. tarentolae. Overexpression of recombinant proteins in transgenic organisms exceeding 10% of total cellular protein, one of the highest overexpression levels obtained in a eukaryotic organism for a cytosolic protein. We show that the linear elements are stably propagated in L. tarentolae cells over long periods of time (>90 generations) without major changes in structure or expression yields. Overexpressing cultures can be obtained without clonal selection of the transfected cells. To establish the utility of the developed system for protein production in a parallelized format, we expressed 37 cytosolic, peripheral, and membrane proteins as fusions with EGFP in L. tarentolae using linear vectors. We detected the expression of 30 of these targets and describe the preparative purification of two arbitrarily selected proteins. Copyright © 2010. Published by Elsevier B.V.
	PMID: 21167214 [PubMed - as supplied by publisher]
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6.	Mol Microbiol. 2011 Jan;79(1):222-39. doi: 10.1111/j.1365-2958.2010.07443.x. Epub 2010 Nov 9. Processing of metacaspase into a cytoplasmic catalytic domain mediating cell death in Leishmania major. Zalila H, González IJ, El-Fadili AK, Delgado MB, Desponds C, Schaff C, Fasel N. Department of Biochemistry, University of Lausanne, 155 Chemin des Boveresses, 1066 Epalinges, Switzerland. Abstract Metacaspases are cysteine peptidases that could play a role similar to caspases in the cell death programme of plants, fungi and protozoa. The human protozoan parasite Leishmania major expresses a single metacaspase (LmjMCA) harbouring a central domain with the catalytic dyad histidine and cysteine as found in caspases. In this study, we investigated the processing sites important for the maturation of LmjMCA catalytic domain, the cellular localization of LmjMCA polypeptides, and the functional role of the catalytic domain in the cell death pathway of Leishmania parasites. Although LmjMCA polypeptide precursor form harbours a functional mitochondrial localization signal (MLS), we determined that LmjMCA polypeptides are mainly localized in the cytoplasm. In stress conditions, LmjMCA precursor forms were extensively processed into soluble forms containing the catalytic domain. This domain was sufficient to enhance sensitivity of parasites to hydrogen peroxide by impairing the mitochondrion. These data provide experimental evidences of the importance of LmjMCA processing into an active catalytic domain and of its role in disrupting mitochondria, which could be relevant in the design of new drugs to fight leishmaniasis and likely other protozoan parasitic diseases. © 2010 Blackwell Publishing Ltd.
	PMID: 21166905 [PubMed - in process]
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7.	Mol Microbiol. 2011 Jan;79(1):94-108. doi: 10.1111/j.1365-2958.2010.07435.x. Epub 2010 Nov 5. A domino effect in drug action: from metabolic assault towards parasite differentiation.Haanstra JR, Kerkhoven EJ, van Tuijl A, Blits M, Wurst M, van Nuland R, Albert MA, Michels PA, Bouwman J, Clayton C, Westerhoff HV, Bakker BM. Department of Molecular Cell Physiology, Faculty of Earth and Life Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1085, NL-1081 HV Amsterdam, the Netherlands. Institute of Biomedical and Life Sciences, Division of Infection and Immunity, University of Glasgow, Glasgow, UK. Zentrum für Molekulare Biologie, Universität Heidelberg, Heidelberg, Germany. Research Unit for Tropical Diseases, de Duve Institute and Laboratory of Biochemistry, Université catholique de Louvain, Brussels, Belgium. AstraZeneca Chair for Systems Biology, Manchester Centre for Integrative Systems Biology, Manchester, UK. Department of Pediatrics, Centre for Liver, Digestive and Metabolic Diseases University Medical Centre Groningen, University Groningen Hanzeplein 1, NL-9713 GZ Groningen, the Netherlands. Abstract Awareness is growing that drug target validation should involve systems analysis of cellular networks. There is less appreciation, though, that the composition of networks may change in response to drugs. If the response is homeostatic (e.g. through upregulation of the target protein), this may neutralize the inhibitory effect. In this scenario the effect on cell growth and survival would be less than anticipated based on affinity of the drug for its target. Glycolysis is the sole free-energy source for the deadly parasite Trypanosoma brucei and is therefore a possible target pathway for anti-trypanosomal drugs. Plasma-membrane glucose transport exerts high control over trypanosome glycolysis and hence the transporter is a promising drug target. Here we show that at high inhibitor concentrations, inhibition of trypanosome glucose transport causes cell death. Most interestingly, sublethal concentrations initiate a domino effect in which network adaptations enhance inhibition. This happens via (i) metabolic control exerted by the target protein, (ii) decreases in mRNAs encoding the target protein and other proteins in the same pathway, and (iii) partial differentiation of the cells leading to (low) expression of immunogenic insect-stage coat proteins. We discuss how these 'anti-homeostatic' responses together may facilitate killing of parasites at an acceptable drug dosage. © 2010 Blackwell Publishing Ltd.
	PMID: 21166896 [PubMed - as supplied by publisher]
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8.	J Parasitol. 2007 Aug;93(4):932-3. Multiplication of Trypanosoma pacifica (Euglenozoa: Kinetoplastea) in English sole, Parophrys vetulus, from Oregon coastal waters. Burreson EM, Karlsbakk E. Virginia Institute of Marine Science, College of William and Mary, Gloucester Point, Virginia 23062, USA. gene@vims.edu Abstract Multiplication of Trypanosoma pacifica was common in the fish host from observations of live flagellates and Giemsa-stained blood smears. Multiplication began with the elongation of the kinetoplast, thickening of the posterior portion of the body, and appearance of a new flagellum near the kinetoplast. The new flagellum was very rigid when less than 3 microm in length, but it became flexible as it elongated. When the new flagellum was approximately 12 microm in length, cell division began and the kinetoplast also began to divide. The timing of nuclear division was variable. Generally, it did not occur until division of the kinetoplast had begun, but occasionally binucleate individuals were observed before cell or kinetoplast division was apparent. As division continued, 1 nucleus migrated past the dividing kinetoplast into the future daughter trypanosome. Finally, the kinetoplast completed division and the trypanosomes separated. Cell division was unequal, with the daughter trypanosome being smaller than the parent and with a more weakly developed undulating membrane.
	PMID: 17918378 [PubMed - indexed for MEDLINE]
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