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Sent on Saturday, 2011 Apr 30Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | Mol Biosyst. 2011 Apr 28. [Epub ahead of print]Molecular adaptability of nucleoside diphosphate kinase b from trypanosomatid parasites: stability, oligomerization and structural determinants of nucleotide binding.Souza TA, Trindade DM, Tonoli CC, Santos CR, Ward RJ, Arni RK, Oliveira AH, Murakami MT.SourceLaboratório Nacional de Biociências (LNBio), Laboratório Nacional de Luz Síncrotron (LNLS), Centro Nacional de Pesquisa em Energia e Materiais (CNPEM), Campinas, SP, Brazil. tatiana.brasil@lnbio.org.br daniel.trindade@lnbio.org.br celisa.tonoli@lnbio.org.br camila.santos@lnbio.org.br mario.murakami@lnbio.org.br. AbstractNucleoside diphosphate kinases play a crucial role in the purine-salvage pathway of trypanosomatid protozoa and have been found in the secretome of Leishmania sp., suggesting a function related to host-cell integrity for the benefit of the parasite. Due to their importance for housekeeping functions in the parasite and by prolonging the life of host cells in infection, they become an attractive target for drug discovery and design. In this work, we describe the first structural characterization of nucleoside diphosphate kinases b from trypanosomatid parasites (tNDKbs) providing insights into their oligomerization, stability and structural determinants for nucleotide binding. Crystallographic studies of LmNDKb when complexed with phosphate, AMP and ADP showed that the crucial hydrogen-bonding residues involved in the nucleotide interaction are fully conserved in tNDKbs. Depending on the nature of the ligand, the nucleotide-binding pocket undergoes conformational changes, which leads to different cavity volumes. SAXS experiments showed that tNDKbs, like other eukaryotic NDKs, form a hexamer in solution and their oligomeric state does not rely on the presence of nucleotides or mimetics. Fluorescence-based thermal-shift assays demonstrated slightly higher stability of tNDKbs compared to human NDKb (HsNDKb), which is in agreement with the fact that tNDKbs are secreted and subjected to variations of temperature in the host cells during infection and disease development. Moreover, tNDKbs were stabilized upon nucleotide binding, whereas HsNDKb was not influenced. Contrasts on the surface electrostatic potential around the nucleotide-binding pocket might be a determinant for nucleotide affinity and protein stability differentiation. All these together demonstrated the molecular adaptation of parasite NDKbs in order to exert their biological functions intra-parasite and when secreted by regulating ATP levels of host cells. |
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| 2. | J Med Microbiol. 2011 Apr 28. [Epub ahead of print]Generation and evaluation of A2-expressing Lactococcus lactis live vaccines against Leishmania donovani in BALB/c mice.Yam KK, Hugentobler F, Pouliot P, Stern AM, Lalande JD, Matlashewski G, Olivier M, Cousineau B.SourceMcGill University. AbstractLeishmaniasis is a parasitic disease affecting over 12 million individuals worldwide. Since current treatments are insufficient, the development of an effective vaccine is a priority. We generated and assessed the efficacy of Leishmania vaccines engineered from the non-colonizing, non-pathogenic Gram-positive bacterium Lactococcus lactis. A truncated, codon-optimized version of the A2 antigen from Leishmania donovani was engineered for expression in L. lactis at three different subcellular compartments: the cytoplasm, secreted outside the cell, or anchored to the cell-wall. These three A2-expressing L. lactis strains were tested for their ability to generate A2-specific immune responses and as live vaccines against visceral L. donovani infection in BALB/c mice. Subcutaneous immunization with live L. lactis expressing A2 anchored to the cell-wall effectively induced high levels of antigen-specific serum antibodies. We demonstrate that L. lactis-based vaccines are a feasible approach in the generation of live vaccines against leishmaniasis. The L. lactis strains generated in this study provide an excellent foundation for further studies on live bacterial vaccines against leishmaniasis and other pathogens. |
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| 3. | J Ethnopharmacol. 2011 Apr 16. [Epub ahead of print]Antiprotozoal activities of traditional medicinal plants from the Garhwal region of North West Himalaya, India.Dua VK, Verma G, Agarwal DD, Kaiser M, Brun R.SourceNational Institute of Malaria Research, Field Unit, Hardwar 249403, India; National Institute of Malaria Research, Sector-8, Dwarka, Delhi 110077, India. AbstractAIM OF THE STUDY:In a search for new plant-derived biologically active compounds against protozoan parasites, an ethnopharmacological study was carried out to evaluate extracts from selected 17 traditional medicinal plants which were used by healers from the Garhwal region of North West Himalaya for the treatment of protozoal infections and fever including malaria. MATERIALS AND METHODS:In vitro activity against erythrocytic stages of Plasmodium falciparum was determined using a modified [3H]-hypoxanthine incorporation assay with the chloroquine- and pyrimethamine-resistant K1 strain. Activity against Trypanosoma brucei rhodesiense was performed on the STIB 900 strain and activity against Trypanosoma cruzi on infected rat skeletal myoblasts (L6 cells) seeded in 96-well microtitre plates while amastigotes of Leishmania donovani strain MHOM/ET/67/L82 were used to assess activity against Leishmania donovani. Cytotoxicity assays were performed against rat skeletal myoblasts (L6-cells). RESULTS AND CONCLUSIONS:Extracts of Artemisia roxburghiana, Roylea cinerea, Leucas cephalotes, Nepeta hindostana and Viola canescens showed good antiplasmodial activity (IC50<5μg/ml). The chloroform extract of Artemisia roxburghiana was the most active (IC50 value of 0.42μg/ml) and the most selective (SI=78) extract for Plasmodium falciparum among all plants extracts examined. The chloroform extract of Leucas cephalotes and the petroleum ether extract of Viola canescens exhibited substantial activities against Leishmania donovani with IC50 values of 3.61μg/ml (SI=8) and 0.40μg/ml (SI=30), respectively. The petroleum ether extract of Viola canescens exhibited activity against Trypanosoma cruzi with an IC50 value of 1.86μg/ml (SI=7). Methanol and water extracts from all plants under investigation were found inactive against all parasites tested. These results support investigation of components of traditional medicines as potential new antiprotozoal agents. On the other hand since herbalism has become the main stream throughout the world, investigation demonstrates that these non-polar plant extracts of six of the plants examined in this study could play an important role in herbal formulations for the treatment of vector borne protozoal diseases. Copyright © 2011. Published by Elsevier Ireland Ltd. |
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| 4. | Vaccine. 2011 Apr 25. [Epub ahead of print]Leishmania major MAP kinase 10 is protective against experimental L. major infection.Kumari S, Singh S, Saha B, Paliwal PK.SourceNational Centre for Cell Science, Ganeshkhind, Pune 411007, India. AbstractLeishmania, a protozoan parasite that resides and replicates obligatorily within macrophages, inflicts a complex of severe diseases known as leishmaniasis. The diseases have significant socio-economic impact through gross disfiguration, morbidity and mortality worldwide. Despite these problems, an effective anti-leishmanial vaccine remains elusive. Herein, we have analyzed the immunogenicity and protective efficacy of L. major MAP kinase 10 (LmjMAPK10) against the challenge infection with the parasite. We observe significant protection against the infection by LmjMAPK10 priming of BALB/c mouse strain, a susceptible host. The resistance to the infection is generally associated with mixed Th1/Th2 responses to the infection following immunization with LmjMAPK10 DNA or protein or a combination of both DNA and protein. Therefore, LmjMAPK10 is a probable vaccine candidate against the infection. Copyright © 2011. Published by Elsevier Ltd. |
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| 5. | Dev Comp Immunol. 2011 Apr 19. [Epub ahead of print]Occurrence of a conserved domain in ATP diphosphohydrolases from pathogenic organisms associated to antigenicity in human parasitic diseases .Maia AC, Detoni ML, Porcino GN, Soares TV, do Nascimento Gusmão MA, Fessel MR, Marques MJ, Souza MA, Coelho PM, Estanislau JA, da Costa Rocha MO, de Oliveira Santos M, Faria-Pinto P, Vasconcelos EG.SourceDepartamento de Bioquímica, Universidade Federal de Juiz de Fora, Juiz de Fora, MG, Brazil; Pós-Graduação em Imunologia e Doenças Infecto-Parasitárias/Genética e Biotecnologia, Instituto de Ciências Biológicas, Universidade Federal de Juiz de Fora, Juiz de Fora, MG, Brazil. AbstractA polypeptide (r78-117) belonging to the potato apyrase was identified as a conserved domain shared with apyrase-like proteins from distinct pathogenic organisms, and was obtained as a 6xHis tag polypeptide (r-Domain B). By ELISA, high IgG, and IgG1 and IgG2a subtypes levels were detected in BALB/c mice pre-inoculated with r-Domain B. In Schistosoma mansoni adult worm or Leishmania (V.) braziliensis promastigote preparation, anti-r-Domain B antibodies inhibit 22-72% of the phosphohydrolytic activities and when immobilized on Protein A-Sepharose immunoprecipitate 42-91% of them. Western blots of the immunoprecipitated resin-antibody-antigen complexes identified bands of mw similar to those predicted for parasite proteins. Total IgG and subclasses of patients with leishmaniasis or schistosomiasis exhibited cross-immunoreactivity with r-Domain B. Therefore, the domain B within both S. mansoni SmATPDase 2 (r156-195) and L. (V.) braziliensis NDPase (r83-122) are potentially involved in the host immune response, and also seem to be conserved during host and parasites co-evolution. Copyright © 2011. Published by Elsevier Ltd. |
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