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Sent on Wednesday, 2012 February 01Search: kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | PLoS Negl Trop Dis. 2012 Jan;6(1):e1469. Epub 2012 Jan 24.Impact of Continuous Axenic Cultivation in Leishmania infantum Virulence.Moreira D, Santarém N, Loureiro I, Tavares J, Silva AM, Amorim AM, Ouaissi A, Cordeiro-da-Silva A, Silvestre R.SourceParasite Disease Group, IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal. AbstractExperimental infections with visceral Leishmania spp. are frequently performed referring to stationary parasite cultures that are comprised of a mixture of metacyclic and non-metacyclic parasites often with little regard to time of culture and metacyclic purification. This may lead to misleading or irreproducible experimental data. It is known that the maintenance of Leishmania spp. in vitro results in a progressive loss of virulence that can be reverted by passage in a mammalian host. In the present study, we aimed to characterize the loss of virulence in culture comparing the in vitro and in vivo infection and immunological profile of L. infantum stationary promastigotes submitted to successive periods of in vitro cultivation. To evaluate the effect of axenic in vitro culture in parasite virulence, we submitted L. infantum promastigotes to 4, 21 or 31 successive in vitro passages. Our results demonstrated a rapid and significant loss of parasite virulence when parasites are sustained in axenic culture. Strikingly, the parasite capacity to modulate macrophage activation decreased significantly with the augmentation of the number of in vitro passages. We validated these in vitro observations using an experimental murine model of infection. A significant correlation was found between higher parasite burdens and lower number of in vitro passages in infected Balb/c mice. Furthermore, we have demonstrated that the virulence deficit caused by successive in vitro passages results from an inadequate capacity to differentiate into amastigote forms. In conclusion, our data demonstrated that the use of parasites with distinct periods of axenic in vitro culture induce distinct infection rates and immunological responses and correlated this phenotype with a rapid loss of promastigote differentiation capacity. These results highlight the need for a standard operating protocol (SOP) when studying Leishmania species. |
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| 2. | PLoS One. 2012;7(1):e30746. Epub 2012 Jan 26.Leishmania donovani: Immunostimulatory Cellular Responses of Membrane and Soluble Protein Fractions of Splenic Amastigotes in Cured Patient and Hamsters.Kumari S, Misra P, Tandon R, Samant M, Sundar S, Dube A.SourceParasitology Division, Central Drug Research Institute, CSIR, Lucknow, Uttar Pradesh, India. AbstractVisceral leishmaniasis (VL), caused by the intracellular parasite Leishmania donovani, L. chagasi and L. infantum is characterized by defective cell-mediated immunity (CMI) and is usually fatal if not treated properly. An estimated 350 million people worldwide are at risk of acquiring infection with Leishmania parasites with approximately 500,000 cases of VL being reported each year. In the absence of an efficient and cost-effective antileishmanial drug, development of an appropriate long-lasting vaccine against VL is the need of the day. In VL, the development of a CMI, capable of mounting Th1-type of immune responses, play an important role as it correlate with recovery from and resistance to disease. Resolution of infection results in lifelong immunity against the disease which indicates towards the feasibility of a vaccine against the disease. Most of the vaccination studies in Leishmaniasis have been focused on promastigote- an infective stage of parasite with less exploration of pathogenic amastigote form, due to the cumbersome process of its purified isolation. In the present study, we have isolated and purified splenic amastigotes of L. donovani, following the traditional protocol with slight modification. These were fractionated into five membranous and soluble subfractions each i.e MAF1-5 and SAF1-5 and were subjected for evaluation of their ability to induce cellular responses. Out of five sub-fractions from each of membrane and soluble, only four viz. MAF2, MAF3, SAF2 and SAF3 were observed to stimulate remarkable lymphoproliferative, IFN-γ, IL-12 responses and Nitric Oxide production, in Leishmania-infected cured/exposed patients and hamsters. Results suggest the presence of Th-1 type immunostimulatory molecules in these sub-fractions which may further be exploited for developing a successful subunit vaccine from the less explored pathogenic stage against VL. |
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| 3. | J Infect Dis. 2012 Jan 30. [Epub ahead of print]Pharmacolog ical Validation of Trypanosoma brucei Phosphodiesterases as Novel Drug Targets.de Koning HP, Gould MK, Sterk GJ, Tenor H, Kunz S, Luginbuehl E, Seebeck T.SourceInstitute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, United Kingdom. AbstractThe development of drugs for neglected infectious diseases often uses parasite-specific enzymes as targets. We here demonstrate that parasite enzymes with highly conserved human homologs may represent a promising reservoir of new potential drug targets. The cyclic nucleotide-specific phosphodiesterases (PDEs) of Trypanosoma brucei, causative agent of the fatal human sleeping sickness, are essential for the parasite. The highly conserved human homologs are well-established drug targets. We here describe what is to our knowledge the first pharmacological validation of trypanosomal PDEs as drug targets. High-throughput screening of a proprietary compound library identified a number of potent hits. One compound, the tetrahydrophthalazinone compound A (Cpd A), was further characterized. It causes a dramatic increase of intracellular cyclic adenosine monophosphate (cAMP). Short-term cell viability is not affected, but cell proliferation is inhibited immediately, and cell death occurs within 3 days. Cpd A prevents cytokinesis, resulting in multinucleated, multiflagellated cells that eventually lyse. These observations pharmacologically validate the highly conserved trypanosomal PDEs as potential drug targets. |
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| 4. | Genomics Proteomics Bioinformatics. 2011 Dec;9(6):218-28.Comparative multivariate analysis of codon and amino Acid usage in three leishmania genomes.Chauhan N, Vidyarthi AS, Poddar R.SourceDepartment of Biotechnology, Birla Institute of Technology, Mesra, Ranchi-835215, India. AbstractMultivariate analysis of codon and amino acid usage was performed for three Leishmania species, including L. donovani, L. infantum and L. major. It was revealed that all three species are under mutational bias and translational selection. Lower GC(12) and higher GC(3S) in all three parasites suggests that the ancestral highly expressed genes (HEGs), compared to lowly expressed genes (LEGs), might have been rich in AT-content. This also suggests that there must have been a faster rate of evolution under GC-bias in LEGs. It was observed from the estimation of synonymous/non-synonymous substitutions in HEGs that the HEG dataset of L. donovani is much closer to L. major evolutionarily. This is also supported by the higher d(N) value as compared to d(S) between L. donovani and L. major, suggesting the conservation of synonymous codon positions between these two species and the role of translational selection in shaping the composition of protein-coding genes. Copyright © 2011 Beijing Genomics Institute. Published by Elsevier Ltd. All rights reserved. |
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| 5. | Clin Exp Immunol. 2012 Mar;167(3):505-13. doi: 10.1111/j.1365-2249.2011.04536.x.Multifunctional CD4(+) T cells in patients with American cutaneous leishmaniasis.Macedo AB, Sánchez-Arcila JC, Schubach AO, Mendonça SC, Marins-Dos-Santos A, de Fatima Madeira M, Gagini T, Pimentel MI, De Luca PM.SourceLaboratório de Imunoparasitologia Plataforma de Citometria de Fluxo, Instituto Oswaldo Cruz Laboratório de Vigilância em Leishmanioses, Instituto de Pesquisa Clínica Evandro Chagas (IPEC), Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil. AbstractLeishmaniasis is a group of important parasitic diseases affecting millions worldwide. To understand more clearly the quality of T helper type 1 (Th1) response stimulated after Leishmania infection, we applied a multiparametric flow cytometry protocol to evaluate multifunctional T cells induced by crude antigen extracts obtained from promastigotes of Leishmania braziliensis (LbAg) and Leishmania amazonensis (LaAg) in peripheral blood mononuclear cells from healed cutaneous leishmaniasis patients. Although no significant difference was detected in the percentage of total interferon (IFN)-γ-producing CD4(+) T cells induced by both antigens, multiparametric flow cytometry analysis revealed clear differences in the quality of Th1 responses. LbAg induced an important proportion of multifunctional CD4(+) T cells (28% of the total Th1 response evaluated), whereas LaAg induced predominantly single-positive cells (68%), and 57% of those were IFN-γ single-positives. Multifunctional CD4(+) T cells showed the highest mean fluorescence intensity (MFI) for the three Th1 cytokines assessed and MFIs for IFN-γ and interleukin-2 from those cells stimulated with LbAg were significantly higher than those obtained after LaAg stimulation. These major differences observed in the generation of multifunctional CD4(+) T cells suggest that the quality of the Th1 response induced by L. amazonensis antigens can be involved in the mechanisms responsible for the high susceptibility observed in L. amazonensis-infected individuals. Ultimately, our results call attention to the importance of studying a Th1 response regarding its quality, not just its magnitude, and indicate that this kind of evaluation might help understanding of the complex and diverse immunopathogenesis of American tegumentary leishmaniasis. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology. |
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| 6. | Mol Microbiol. 2012 Jan 31. doi: 10.1111/j.1365-2958.2012.07978.x. [Epub ahead of print]Involvement of TatD nuclease during programmed cell death in the protozoan parasite Trypanosoma brucei.Gannavaram S, Debrabant A.SourceLaboratory of Emerging Pathogens, Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, US Food and Drug Administration, Bethesda, MD 20892, USA. AbstractIn this report, we describe the involvement of TatD nuclease during programmed cell death (PCD) in the human protozoan parasite Trypanosoma brucei. T. brucei TatD nuclease showed intrinsic DNase activity, was localized in the cytoplasm and translocated to the nucleus when cells were treated with inducers previously demonstrated to cause PCD in T. brucei. Overexpression of TatD nuclease resulted in elevated PCD and conversely, loss of TatD expression by RNAi conferred significant resistance to the induction of PCD in T. brucei. Co-immunoprecipitation studies revealed that TatD nuclease interacts with endonucleaseG suggesting that these two nucleases could form a DNA degradation complex in the nucleus. Together, biochemical activity, RNAi and subcellular localization results demonstrate the role of TatD nuclease activity in DNA degradation during PCD in these evolutionarily ancient eukaryotic organisms. Further, in conjunction with endonucleaseG, TatD may represent a critical nuclease in a caspase-independent PCD pathway in trypanosomatid parasites since caspases have not been identified in these organisms. Published 2012. This article is a U.S. Government work and is in the public domain in the USA. |
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| 7. | Ann Trop Med Parasitol. 2011 Sep;105(6):425-30.Lack of assoc iation between blood-based detection of Trypanosoma cruzi DNA and cardiac involvement in a non-endemic area.Norman FF, Pérez-Ayala A, Pérez-Molina JA, Flores-Chavez M, Cañavate C, López-Vélez R.SourceTropical Medicine and Clinical Parasitology, Infectious Diseases Department, Hospital Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria, Madrid, Spain. ffnorman@gmail.com AbstractCases of chronic Chagas disease have been increasing in non-endemic areas due to the growth in immigration. This study examined the association between positive Trypanosoma cruzi-DNA detection in blood by PCR and presence of chagasic cardiac involvement in a cohort of immigrants in a European city. No association was found in this study between the positive T. cruzi blood PCR and cardiac involvement. |
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