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Sent on Thursday, 2010 Jan 21Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | Immunol Res. 2010 Jan 20. [Epub ahead of print]Immune evasive mechanisms contributing to persistent Leishmania donovani infection.Stäger S, Joshi T, Bankoti R.Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, BRB, Rm 655, 733 N. Broadway, Baltimore, MD, 21205, USA, sstager1@jhmi.edu. The protozoan parasite Leishmania donovani, a causative agent of visceral leishmaniasis, has evolved several strategies to interfere with the immune system and establish persistent infections that are potentially lethal. In this article, we discuss two mechanisms of immune evasion adopted by the parasite: the induction of immune suppressive IL-10 responses and the generation of poor and functionally impaired CD8(+) T-cell responses. |
| PMID: 20087685 [PubMed - as supplied by publisher] | |
| 2. | Mol Cell Biol. 2010 Jan 19. [Epub ahead of print]RET1-catalyzed Uridylylation Shapes the Mitochondrial Transcriptome in Trypanosoma brucei.Aphasizheva I, Aphasizhev R.Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, CA 92697, USA. RNA uridylylation is critical for the expression of the mitochondrial genome in trypanosomes. Short U-tails are added to guide RNAs and ribosomal RNAs while long A/U heteropolymers mark 3'-ends of most messenger RNAs. Three divergent mitochondrial terminal uridylyl transferases (TUTases) are known: RET1 catalyzes gRNA uridylylation, RET2 executes U-insertion mRNA editing and MEAT1 associates with the editosome-like complex. However, the activities responsible for 3'-uridylylation of rRNAs and mRNAs, and the roles of these modifications are unclear. To dissect the functions of mitochondrial TUTases, we investigated the effects of their repression and overexpression on abundance, processing, 3'-end status, and in vivo stability of major mitochondrially-encoded RNA classes. We show that RET1 adds U-tails to gRNA, rRNAs and select mRNAs, and contributes Us into A/U-heteropolymers. Furthermore, RET1's TUTase activity is required the nucleolytic processing of gRNA, rRNA and mRNA precursors. The U-tail's presence does not affect the stability of gRNAs and rRNAs, while transcript-specific uridylylation triggers 3'-5' mRNA decay. We propose that the minicircle-encoded anti-sense transcripts, which are stabilized by RET1-catalyzed uridylylation, may direct a nucleolytic cleavage of multicistronic precursors. |
| PMID: 20086102 [PubMed - as supplied by publisher] | |
| 3. | Infect Immun. 2010 Jan 19. [Epub ahead of print]Differential host responses to Trypanosoma brucei infection: a role for parasite genetic diversity.Morrison LJ, McLellan S, Sweeney L, Chan C, Macleod A, Tait A, Turner CM.Wellcome Trust Centre for Molecular Parasitology, University of Glasgow, Biomedical Research Centre, 120 University Place, Glasgow G12 8TA, United Kingdom; Division of Infection and Immunity, Faculty of Biomedical and Life Sciences, University of Glasgow, Biomedical Research Centre, 120 University Place, Glasgow G12 8TA, United Kingdom. The post-genomic era has revolutionised approaches to defining host-pathogen interactions, and the investigation of the influence of genetic variation in either protagonist upon infection outcome. We analysed pathology induced by infection with two genetically distinct Trypanosoma brucei strains, and found that pathogenesis is partly strain-specific involving distinct host mechanisms. Infections of BALB/c mice with one strain (927) resulted in more severe anaemia and greater erythropoietin production compared to infections with the second strain (247), which, contrastingly, displayed greater splenomegaly and reticulocytosis. Plasma IL-10 and IFN-gamma levels were significantly higher in 927-infected mice, whereas IL-12 was higher in 247 infections. To define mechanisms underlying these differences, expression microarray analysis of host genes in the spleen at day 10 post-infection was undertaken. Rank product analysis (RPA) showed that 40% of significantly differentially expressed genes were specific to infections with one or other trypanosome strain. RPA and Pathway analysis identified LXR/RXR signalling, IL-10 signalling and alternative macrophage activation as the most significantly differentially activated host processes. These data suggest that innate immune response modulation is a key determinant in trypanosome infections, the pattern of which can vary dependent upon trypanosome strain. This strongly suggests a parasite genetic component responsible for causing disease in the host. Our understanding of trypanosome infections is largely based on studies involving single parasite strains, and our results suggest that an integrated host-parasite approach is required for future studies on trypanosome pathogenesis. Furthermore, it will be necessary to incorporate parasite variation in both experimental systems and models of pathogenesis. |
| PMID: 20086091 [PubMed - as supplied by publisher] | |
| 4. | J Cell Sci. 2010 Jan 19. [Epub ahead of print]Membrane protein SMP-1 is required for normal flagellum function in Leishmania.Tull D, Naderer T, Spurck T, Mertens HD, Heng J, McFadden GI, Gooley PR, McConville MJ.Eukaryotic flagella and cilia are surrounded by a membrane that is continuous with, but distinct from, the rest of the plasma membrane. In Leishmania parasites, the inner leaflet of the flagellar membrane is coated with the acylated membrane protein, SMP-1. Here, we provide evidence that SMP-1 stabilizes the flagellar membrane and is required for flagella elongation and function. The expression and flagella targeting of SMP-1 is tightly associated with flagella elongation during amastigote to promastigote differentiation. Deletion of the genes encoding SMP-1 and the flagellar pocket protein SMP-2, led to the production of short flagella and defects in motility. Alterations in the physical properties of the smp-1/smp-2(-/-) flagellar membrane were suggested by: (1 the accumulation of membrane vesicles in the flagellar matrix, and (2 further retraction of flagella following partial inhibition of sterol and sphingolipid biosynthesis. The flagella phenotype of the smp-1/smp-2(-/-) null mutant was reversed by re-expression of SMP-1, but not SMP-2. SMP-1 contains a jelly-roll beta-sheet structure that is probably conserved in all SMP proteins, and forms stable homo-oligomers in vivo. We propose that the SMP-1 coat generates and/or stabilizes sterol- and sphingolipid-rich domains in the flagellar membrane. |
| PMID: 20086045 [PubMed - as supplied by publisher] | |
| 5. | Glycobiology. 2010 Jan 18. [Epub ahead of print]Sialic acids in different Leishmania sp., its correlation with nitric oxide resistance and host responses.Ghoshal A, Gerwig GJ, Kamerling JP, Mandal C.Infectious Disease and Immunology Division, Indian Institute of Chemical Biology, A Unit of Council of Scientific and Industrial Research (C.S.I.R.), Govt. of India, 4 Raja S.C. Mullick Road, Jadavpur, Kolkata-700 032, India. The presence of different derivatives of sialic acids (SA) on Leishmania donovani instigated us to investigate their status on different strains of Leishmania sp. causing different forms of the disease. Leishmania tropica (K27), Leishmania major (JISH118) and Leishmania mexicana (LV4) responsible for cutaneous, Leishmania braziliensis (L280) and Leishmania amazonensis (LV81) causing diffuse and Leishmania infantum (MON29) responsible for visceral leishmaniasis were included in this study. The strains showed a differential distribution of SA in spite of their close resemblance in pathogenesis. K27, JISH118, L280 and MON29 were categorized as high SA-containing strains having enhanced 9-O-acetyl sialic acid (9-O-AcSA(high)) whereas LV4 and LV81 evidenced considerably reduced SA. Interestingly, 9-O-AcSA(high) promastigotes showed significant viability as compared to their de-O-acetylated forms after exposure to NaNO(2) suggesting the involvement of 9-O-AcSA in conferring nitric oxide (NO) resistance. Enhanced intracellular survivability was demonstrated following infection of human macrophages with 9-O-AcSA(high) promastigotes in contrast to their de-O-acetylated forms indicating their contribution in bestowing a survival benefit. Additionally, reduced accumulation of NO, interleukin-12 and interferon-gamma in the supernatant of macrophages infected with 9-O-AcSA(high) promastigotes indicated suppression of leishmanicidal host responses. However, LV4 and LV81 with least 9-O-AcSA, before and after de-O-acetylation, showed unaltered NO resistance, multiplicity and host responses signifying the probable involvement of other determinants which may be a function of their inherent parasitic attribute. Hence, enhanced levels of 9-O-AcSA serve as one of the potential determinants responsible for increased NO resistance and survivability of parasites by inhibition of host responses. |
| PMID: 20085901 [PubMed - as supplied by publisher] | |
| 6. | Int J Parasitol. 2010 Jan 16. [Epub ahead of print]Acetate formation in the energy metabolism of parasitic helminths and protists.Tielens AG, van Grinsven KW, Henze K, van Hellemond JJ, Martin W.Department of Medical Microbiology & Infectious Diseases, Erasmus MC University Medical Center, 's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. Formation and excretion of acetate as a metabolic end product of energy metabolism occurs in many protist and helminth parasites, such as the parasitic helminths Fasciola hepatica, Haemonchus contortus and Ascaris suum, and the protist parasites, Giardia lamblia, Entamoeba histolytica, Trichomonas vaginalis as well as Trypanosoma and Leishmania spp. In all of these parasites acetate is a main end product of their energy metabolism, whereas acetate formation does not occur in their mammalian hosts. Acetate production might therefore harbour novel targets for the development of new anti-parasitic drugs. In parasites, acetate is produced from acetyl-CoA by two different reactions, both involving substrate level phosphorylation, that are catalyzed by either a cytosolic acetyl-CoA synthetase (ACS) or an organellar acetate:succinate CoA-transferase (ASCT). The ACS reaction is directly coupled to ATP synthesis, whereas the ASCT reaction yields succinyl-CoA for ATP formation via succinyl-CoA synthetase (SCS). Based on recent work on the ASCTs of F. hepatica, T. vaginalis and Trypanosoma brucei we suggest the existence of three subfamilies of enzymes within the CoA-transferase family I. Enzymes of these three subfamilies catalyze the ASCT reaction in eukaryotes via the same mechanism, but the subfamilies share little sequence homology. The CoA-transferases of the three subfamilies are all present inside ATP-producing organelles of parasites, those of subfamily IA in the mitochondria of trypanosomatids, subfamily IB in the mitochondria of parasitic worms and subfamily IC in hydrogenosome-bearing parasites. Together with the recent characterization among non-parasitic protists of yet a third route of acetate formation involving acetate kinase (ACK) and phosphotransacetylase (PTA) that was previously unknown among eukaryotes, these recent developments provide a good opportunity to have a closer look at eukaryotic acetate formation. Copyright © 2010. Published by Elsevier Ltd. |
| PMID: 20085767 [PubMed - as supplied by publisher] | |
| 7. | Assay Drug Dev Technol. 2010 Jan 19. [Epub ahead of print]Optimization of a Non-Radioactive High-Throughput Assay for Decarboxylase Enzymes.Smithson DC, Shelat AA, Baldwin J, Phillips MA, Guy RK.Graduate Program in Chemistry and Chemical Biology, University of California, San Francisco, California. , Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee. Herein, we describe the optimization of a linked enzyme assay suitable for high-throughput screening of decarboxylases, a target family whose activity has historically been difficult to quantify. Our approach uses a commercially available bicarbonate detection reagent to measure decarboxylase activity. The assay is performed in a fully enclosed automated screening system under inert nitrogen atmosphere to minimize perturbation by exogenous CO(2). Receiver operating characteristic (ROC) analysis following a pilot screen of a small library of approximately 3,600 unique molecules for inhibitors of Trypanosoma brucei ornithine decarboxylase quantitatively demonstrates that the assay has excellent discriminatory power (area under the curve = 0.90 with 95% confidence interval between 0.82 and 0.97). |
| PMID: 20085486 [PubMed - as supplied by publisher] | |
| 8. | US Army Med Dep J. 2009 Jul-Sep:16-27.Operational vector-borne disease surveillance a nd control: closing the capabilities gap through research at overseas military laboratories.Evans BP, Clark JW, Barbara KA, Mundal KD, Furman BD, McAvin JC, Richardson JH.Department of Entomology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand. Malaria, dengue fever, chikungunya virus, leishmaniasis, and a myriad of other vector-borne diseases pose significant threats to the warfighter and to the overall combat effectiveness of units. Military preventive medicine (PM) assets must accurately evaluate the vector-borne disease threat and then implement and/or advise the commander on countermeasures to reduce a particular threat. The success of these measures is contingent upon the biology of the disease vector and on the tools or methods used to conduct vector/pathogen surveillance and vector control. There is a significant gap between the tools available and those required for operational PM assets to provide real-time, effective surveillance and control. A network of US Army and US Navy overseas laboratories is focused on closing the current capabilities gap. Their mission is to develop and field test tools and methods to enhance the combatant commander's ability to identify and mitigate the threat posed by these vector-borne diseases. |
| PMID: 20084734 [PubMed - in process] | |
| 9. | Parasitol Int. 2009 Dec;58(4):367-74. Epub 2009 Aug 8.Molecular characterization and intracellular distribution of the alpha 5 subunit of Trypanosoma cruzi 20S proteasome.Gutiérrez B, Osorio L, Motta MC, Huima-Byron T, Erdjument-Bromage H, Muñoz C, Sagua H, Mortara RA, Echeverría A, Araya JE, González J.Health Sciences Faculty, University of Antofagasta, Antofagasta, Chile. Three different monoclonal antibodies were produced against Trypanosona cruzi proteasomes. These antibodies were shown to react with a single 27-kDa band on immunoblots of purified proteasomes. Using a 7E5 monoclonal antibody (IgG1) that recognized the alpha5 subunit of protozoan protease we have studied the intracellular distribution of the T. cruzi 20S proteasome. Contrary to all cell types described to date, T. cruzi 20S proteasome was found not only in the cytoplasm and nucleus but also in the kinetoplast. As revealed by confocal microscopy, the reactivity of monoclonal antibody 7E5 was highly specific for protozoan proteasome because the antibody recognized only the proteasomes from parasites and not those from the mammalian host in T. cruzi infected cells. These findings were confirmed by immunoblots or immunoprecipitations, followed by chymotrypsin-like activity detection in kinetoplasts isolated by differential centrifugation and sucrose density gradients. Proteasome 20S was present in all T. cruzi stages and only slight differences in terms of relative abundance were found. The potential role of the proteasome in kinetoplast remodeling remains to be determined. |
| PMID: 19666140 [PubMed - indexed for MEDLINE] | |
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