What's new for 'Trypanosomatids' in PubMed

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Sent on Wednesday, 2012 March 14
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 - 9 of 9

1.	PLoS One. 2012;7(3):e32761. Epub 2012 Mar 6. HIV-1 Promotes Intake of Leishmania Parasites by Enhancing Phosphatidylserine-Mediated, CD91/LRP-1-Dependent Phagocytosis in Human Macrophages. Lodge R, Ouellet M, Barat C, Andreani G, Kumar P, Tremblay MJ. Source Centre de Recherche en Infectiologie, Centre Hospitalier Universitaire de Québec - CHUL, Université Laval, Québec, Canada. Abstract Over the past decade, the number of reported human immunodeficiency virus type-1 (HIV-1)/Leishmania co-infections has risen dramatically, particularly in regions where both diseases are endemic. Although it is known that HIV-1 infection leads to an increase in susceptibility to Leishmania infection and leishmaniasis relapse, little remains known on how HIV-1 contributes to Leishmania parasitaemia. Both pathogens infect human macrophages, and the intracellular growth of Leishmania is increased by HIV-1 in co-infected cultures. We now report that uninfected bystander cells, not macrophages productively infected with HIV-1, account for enhanced phagocytosis and higher multiplication of Leishmania parasites. This effect can be driven by HIV-1 Tat protein and transforming growth factor-beta (TGF-β). Furthermore, we show for the first time that HIV-1 infection increases surface expression of phosphatidylserine receptor CD91/LRP-1 on human macrophages, thereby leading to a Leishmania uptake by uninfected bystander cells in HIV-1-infected macrophage populations. The more important internalization of parasites is due to interactions between the scavenger receptor CD91/LRP-1 and phosphatidylserine residues exposed at the surface of Leishmania. We determined also that enhanced CD91/LRP-1 surface expression occurs rapidly following HIV-1 infection, and is triggered by the activation of extracellular TGF-β. Thus, these results establish an intricate link between HIV-1 infection, Tat, surface CD91/LRP-1, TGF-β, and enhanced Leishmania phosphatidylserine-mediated phagocytosis.
	PMID: 22412921 [PubMed - in process]

2.	PLoS One. 2012;7(3):e32674. Epub 2012 Mar 8. Identification of ORC1/CDC6-Interacting Factors in Trypanosoma brucei Reveals Critical Features of Origin Recognition Complex Architecture. Tiengwe C, Marcello L, Farr H, Gadelha C, Burchmore R, Barry JD, Bell SD, McCulloch R. Source The Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom. Abstract DNA Replication initiates by formation of a pre-replication complex on sequences termed origins. In eukaryotes, the pre-replication complex is composed of the Origin Recognition Complex (ORC), Cdc6 and the MCM replicative helicase in conjunction with Cdt1. Eukaryotic ORC is considered to be composed of six subunits, named Orc1-6, and monomeric Cdc6 is closely related in sequence to Orc1. However, ORC has been little explored in protists, and only a single ORC protein, related to both Orc1 and Cdc6, has been shown to act in DNA replication in Trypanosoma brucei. Here we identify three highly diverged putative T. brucei ORC components that interact with ORC1/CDC6 and contribute to cell division. Two of these factors are so diverged that we cannot determine if they are eukaryotic ORC subunit orthologues, or are parasite-specific replication factors. The other we show to be a highly diverged Orc4 orthologue, demonstrating that this is one of the most widely conserved ORC subunits in protists and revealing it to be a key element of eukaryotic ORC architecture. Additionally, we have examined interactions amongst the T. brucei MCM subunits and show that this has the conventional eukaryotic heterohexameric structure, suggesting that divergence in the T. brucei replication machinery is limited to the earliest steps in origin licensing.
	PMID: 22412905 [PubMed - in process]

3.	PLoS One. 2012;7(3). doi: 10.1371/annotation/aa6cd97c-cfb5-4afe-aa25-f5ecfed07980. Epub 2012 Mar 7. Correction: Cytokinesis in Bloodstream Stage Trypanosoma brucei Requires a Family of Katanins and Spastin. Benz C, Clucas C, Mottram JC, Hammarton TC. Abstract [This corrects the article on p. e30367 in vol. 7.].
	PMID: 22412824 [PubMed - as supplied by publisher]

4.	J Immunol. 2012 Mar 12. [Epub ahead of print] Marginal Zone B Cells Regulate Antigen-Specific T Cell Responses during Infection. Bankoti R, Gupta K, Levchenko A, Stäger S. Source Department of Molecular and Comparative Pathobiology, The Johns Hopkins School of Medicine, Baltimore, MD 21205; Abstract Marginal zone B cells (MZB) participate in the early immune response to several pathogens. In this study, we show that in μMT mice infected with Leishmania donovani, CD8 T cells displayed a greater cytotoxic potential and generated more effector memory cells compared with infected wild type mice. The frequency of parasite-specific, IFN-γ(+) CD4 T cells was also increased in μMT mice. B cells were able to capture parasites, which was associated with upregulation of surface IgM and MyD88-dependent IL-10 production. Moreover, MZB presented parasite Ags to CD4 T cells in vitro. Depletion of MZB also enhanced T cell responses and led to a decrease in the parasite burden but did not alter the generation of effector memory T cells. Thus, MZB appear to suppress protective T cell responses during the early stages of L. donovani infection.
	PMID: 22412197 [PubMed - as supplied by publisher]

5.	Antimicrob Agents Chemother. 2012 Mar 12. [Epub ahead of print] Efficacy of Combined Therapy with Liposome-Encapsulated Meglumine Antimoniate and Allopurinol in the Treatment of Canine Visceral Leishmaniasis. da Silva SM, Amorim IF, Ribeiro RR, Azevedo EG, Demicheli C, Melo MN, Tafuri WL, Gontijo NF, Michalick MS, Frézard F. Source Departamento de Parasitologia. Abstract An innovative liposomal formulation of meglumine antimoniate (LMA) was recently reported to promote both long-term parasite suppression and reduction of infectivity to sand flies in dogs with visceral leishmaniasis. However, five months after treatment, parasites were still found in the bone marrow of all treated dogs. In order to improve treatment with LMA, the present study aimed to evaluate its efficacy in association with allopurinol. Mongrel dogs naturally infected with Leishmania infantum were treated with six doses of LMA (6.5 mg Sb/kg/dose) given with 4-day intervals, plus allopurinol (20 mg/kg/24h per os) during 140 days. Comparison was made with groups treated with LMA, allopurinol, empty liposomes plus allopurinol, empty liposomes and saline. Dogs remained without treatment from day 140 to 200 after the start of treatment. The drug association promoted both clinical improvement of dogs and significant reduction in the parasitic load in bone marrow and spleen on days 140 and 200, compared to pre-treatment period. This is in contrast with the other protocols that did not significantly reduce the bone marrow parasite load on day 200. Strikingly, the combined treatment, in contrast to the other regimens, induced negative qPCR results in the liver of 100% of dogs. Both xenodiagnosis and skin parasite determination by qPCR indicated that the drug association was effective in blocking the transmission of skin parasites to sand flies. Based on all the parasitological tests performed on day 200, 50% of the animals submitted to the combined treatment were considered cured.
	PMID: 22411610 [PubMed - as supplied by publisher]

6.	Adv Exp Med Biol. 2012;729:65-82. Recent developments in the interactions between caveolin and pathogens. Machado FS, Rodriguez NE, Adesse D, Garzoni LR, Esper L, Lisanti MP, Burk RD, Albanese C, Van Doorslaer K, Weiss LM, Nagajyothi F, Nosanchuk JD, Wilson ME, Tanowitz HB. Source Department of Biochemistry and Immunology, Institute for Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil, machadofs@icb.ufmg.br. Abstract The role of caveolin and caveolae in the pathogenesis of infection has only recently been appreciated. In this chapter, we have highlighted some important new data on the role of caveolin in infections due to bacteria, viruses and fungi but with particular emphasis on the protozoan parasites Leishmania spp., Trypanosoma cruzi and Toxoplasma gondii. This is a continuing area of research and the final chapter has not been written on this topic.
	PMID: 22411314 [PubMed - in process]

7.	Acta Trop. 2012 Mar 3. [Epub ahead of print] Environmental factors underlying spatial patterns of sand flies (Diptera: Psychodidae) associated with leishmaniasis in Southern Sinai, Egypt. Kassem HA, Siri J, Kamal HA, Wilson ML. Source Institute of Environmental Studies and Research, Ain Shams University, Abbassia, Postal Code 11566 Cairo, Egypt. Abstract Although Leishmania major is endemic in parts of the Sinai of Egypt, the ecology and distribution of Leishmania sand fly vectors in southern Sinai has not been well characterized. Accordingly, additional sand fly samples were obtained at 41 sites in the southern Sinai region during 1996-1997, and analyzed to improve the characterization of risk of sand fly-borne pathogens. Using a Geographic Information System (GIS), species-specific spatial distributions that might suggest zoonotic cutaneous leishmaniasis (ZCL) risk areas were determined in relation to contextual environmental factors, including geology, hydrogeology, climate variables and elevation. Southern Sinai was characterized by a diverse sand fly fauna (eight Phlebotomus species), probably attributable to highly variable landscape and environmental factors. Phlebotomus alexandri, Phlebotomus kazeruni and Phlebotomus sergenti were widespread and abundant, Phlebotomus papatasi and Phlebotomus bergeroti were less frequent, and Phlebotomus arabicus, Phlebotomus major and Phlebotomus orientalis had highly restricted distributions. Logistic regression models indicated that elevation and climatic conditions were limiting determinants for the distributions of sand flies in southern Sinai. Based on the predicted distribution of P. papatasi, a recognized vector of L. major, about one-quarter of southern Sinai may be at high risk of ZCL. Risk areas for the suspected ZCL vector P. bergeroti had a more patchy distribution. Results suggest that future studies should include other factors related to vector abundance, vector competence, human population, and parasite and reservoir host(s) to produce more comprehensive ZCL transmission risk maps, thus helping in planning effective prevention and control strategies. Copyright © 2012. Published by Elsevier B.V.
	PMID: 22410540 [PubMed - as supplied by publisher]

8.	Anal Biochem. 2012 Mar 9. [Epub ahead of print] A fluorescence polarization binding assay to identify inhibitors of flavin-dependent monooxygenases. Qi J, Kizjakina K, Robinson R, Tolani K, Sobrado P. Source Department of Biochemistry, Virginia Tech, Blacksburg, VA 24061; Enzyme Research and Drug Discovery Laboratory, Virginia Tech, Blacksburg, VA 24061. Abstract N-hydroxylating monooxygenases (NMOs) are essential for pathogenesis in fungi and mycobacteria. NMOs catalyze the hydroxylation of lysine and ornithine in the biosynthesis of hydroxamate-containing siderophores. Inhibition of kynurenine monooxygenase (KMO), which catalyzes the conversion of L-kynurenine to 3-hydroxykynurenine, alleviates neurodegenerative disorders such as Huntington's and Alzheimer's diseases and brain infections caused by the parasite Trypanosoma brucei. These enzymes are examples of flavin-dependent monooxygenases, which are validated drug targets. Here, we describe the development and optimization of a fluorescence polarization assay to identify potential inhibitors of flavin monooxygenases. Fluorescently-labeled ADP molecules were synthesized and tested. An ADP-TAMRA chromophore bound to KMO with a K(d) value of 0.60 ± 0.05 μM and to the NMOs from Aspergillus fumigatus and Mycobacterium smegmatis with K(d) values of 2.1 ± 0.2 μM and 4.0 ± 0.2 μM, respectively. The assay was tested in competitive binding experiments with substrates and products of KMO and an NMO. Furthermore, we showed that this assay can be used to identify inhibitors of NMOs. A Z'-factor of 0.77 was calculated and we show that the assay exhibits good tolerance to temperature, incubation time, and DMSO concentration. Copyright © 2012. Published by Elsevier Inc.
	PMID: 22410281 [PubMed - as supplied by publisher]

9.	Future Microbiol. 2011 Dec;6(12):1521-33. The role of Toll-like receptors and adaptive immunity in the development of protective or pathological immune response triggered by the Trypanosoma cruzi protozoan. Pellegrini A, Guiñazu N, Giordanengo L, Cano RC, Gea S. Source Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, CIBICI-CONICET, Universidad Nacional de Córdoba, Ciudad Universitaria, Córdoba 5000, Argentina. Abstract Trypanosoma cruzi, the causal agent of Chagas disease, is an intracellular protozoan parasite that predominantly invades macrophages and cardiomyocytes, leading to persistent infection. Several members of the Toll-like receptor family are crucial for innate immunity to infection and are involved in maintaining tissue homeostasis. This review focuses on recent experimental findings of the innate and adaptive immune response in controlling the parasite and/or in generating heart and liver tissue injury. We also describe the importance of the host's genetic background in the outcome of the disease and emphasize the importance of studying the response to specific parasite antigens. Understanding the dual participation of the immune response may contribute to the design of new therapies for Chagas disease.
	PMID: 22122446 [PubMed - indexed for MEDLINE]
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