What's new for 'Trypanosomatids' in PubMed

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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 - 10 of 12

1.	PLoS Negl Trop Dis. 2010 Oct 5;4(10). pii: e842. Identification of Leishmania Proteins Preferentially Released in Infected Cells Using Change Mediated Antigen Technology (CMAT). Kima PE, Bonilla JA, Cho E, Ndjamen B, Canton J, Leal N, Handfield M. Department of Microbiology and Cell Science, University of Florida, Gainesville, Florida, United States of America. Abstract Although Leishmania parasites have been shown to modulate their host cell's responses to multiple stimuli, there is limited evidence that parasite molecules are released into infected cells. In this study, we present an implementation of the change mediated antigen technology (CMAT) to identify parasite molecules that are preferentially expressed in infected cells. Sera from mice immunized with cell lysates prepared from L. donovani or L. pifanoi-infected macrophages were adsorbed with lysates of axenically grown amastigotes of L. donovani or L. pifanoi, respectively, as well as uninfected macrophages. The sera were then used to screen inducible parasite expression libraries constructed with genomic DNA. Eleven clones from the L. pifanoi and the L. donovani screen were selected to evaluate the characteristics of the molecules identified by this approach. The CMAT screen identified genes whose homologs encode molecules with unknown function as well as genes that had previously been shown to be preferentially expressed in the amastigote form of the parasite. In addition a variant of Tryparedoxin peroxidase that is preferentially expressed within infected cells was identified. Antisera that were then raised to recombinant products of the clones were used to validate that the endogenous molecules are preferentially expressed in infected cells. Evaluation of the distribution of the endogenous molecules in infected cells showed that some of these molecules are secreted into parasitophorous vacuoles (PVs) and that they then traffic out of PVs in vesicles with distinct morphologies. This study is a proof of concept study that the CMAT approach can be applied to identify putative Leishmania parasite effectors molecules that are preferentially expressed in infected cells. In addition we provide evidence that Leishmania molecules traffic out of the PV into the host cell cytosol and nucleus.
	PMID: 20957202 [PubMed - in process]
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2.	PLoS Negl Trop Dis. 2010 Oct 5;4(10). pii: e832. Enhanced Case Detection and Improved Diagnosis of PKDL in a Kala-azar-Endemic Area of Bangladesh. Mondal D, Nasrin KN, Huda MM, Kabir M, Hossain MS, Kroeger A, Thomas T, Haque R. Parasitology Laboratory, Laboratory Sciences Division, International Centre for Diarrhoeal Diseases Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh. Abstract OBJECTIVES: To support the Bangladesh National Kala-azar Elimination Programme (NKEP), we investigated the feasibility of using trained village volunteers for detecting post-kala-azar dermal leishmaniasis (PKDL) cases, using polymerase chain reaction (PCR) for confirmation of diagnosis and treatment compliance by PKDL patients in Kanthal union of Trishal sub-district, Mymensingh, Bangladesh. METHODS: In this cross-sectional study, Field Research Assistants (FRAs) conducted census in the study area, and the research team trained village volunteers on how to look for PKDL suspects. The trained village volunteers (TVVs) visited each household in the study area for PKDL suspects and referred the suspected PKDL cases to the study clinic. The suspected cases underwent physical examinations by a qualified doctor and rK39 strip testing by the FRAs and, if positive, slit skin examination (SSE), culture, and PCR of skin specimens and peripheral buffy coat were done. Those with evidence of Leishmania donovani (LD) were referred for treatment. All the cases were followed for one year. RESULTS: The total population of the study area was 29,226 from 6,566 households. The TVVs referred 52 PKDL suspects. Probable PKDL was diagnosed in 18 of the 52 PKDL suspect cases, and PKDL was confirmed in 9 of the 18 probable PKDL cases. The prevalence of probable PKDL was 6.2 per 10,000 people in the study area. Thirteen PKDL suspects self-reported from outside the study area, and probable and confirmed PKDL was diagnosed in 10 of the 13 suspects and in 5 of 10 probable PKDL cases respectively. All probable PKDL cases had hypopigmented macules. The median time for PKDL development was 36 months (IQR, 24-48). Evidence of the LD parasite was documented by SSE and PCR in 3.6% and 64.3% of the cases, respectively. PCR positivity was associated with gender and severity of disease. Those who were untreated had an increased risk (odds ratio = 3.33, 95%CI 1.29-8.59) of having persistent skin lesions compared to those who were treated. Patients' treatment-seeking behavior and treatment compliance were poor. CONCLUSION: Improved detection of PKDL cases by TVVs is feasible and useful. The NKEP should promote PCR for the diagnosis of PKDL and should find ways for improving treatment compliance by patients.
	PMID: 20957193 [PubMed - in process]
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3.	Antimicrob Agents Chemother. 2010 Oct 18. [Epub ahead of print] Differential effects of paromomycin on ribosomes of Leishmania mexicana and mammalian cells. Fernández MM, Malchiodi EL, Algranati ID. Cátedra de Inmunología and Instituto de Estudios de la Inmunidad Humoral (IDEHU), CONICET-UBA, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires; and Fundación Instituto Leloir, Patricias Argentinas 435, 1405 Buenos Aires, Argentina. Abstract Paromomycin, an aminoglycoside antibiotic having low mammalian cell toxicity, is one of the drugs currently used in the chemotherapy of cutaneous and visceral leishmaniasis. In order to understand the mode of action of this antibiotic at molecular level, we have investigated the effects of paromomycin on protein synthesis in Leishmania and its mammalian hosts. We were able to demonstrate that in vivo protein synthesis in the promastigote stage of the parasite and its proliferation rate are markedly inhibited by paromomycin, while only slightly affected by other aminoglycoside antibiotics such as streptomycin and neomycin B. Furthermore, both in vitro polypeptide synthesis induced by poly-U as messenger RNA as well as accuracy of translation are significantly decreased by paromomycin in cell-free systems containing ribosomal particles of Leishmania promastigotes. Conversely, when ribosomes from mammalian cells are used instead of the protozoan particles, polyphenylalanine synthesis is only barely reduced by the antibiotic and the translation misreading remains almost unaltered. Surface plasmon resonance analysis of the interaction between paromomycin and protozoan or mammalian cell ribosomal RNAs shows a strong antibiotic binding to the parasite ribosomal decoding site and practically no interaction with the mammalian cell counterpart. Our results indicating differential effects of paromomycin on the translation processes of the Leishmania parasite and its mammalian hosts can explain the therapeutic efficiency of this antibiotic as an antileishmaniasis agent.
	PMID: 20956601 [PubMed - as supplied by publisher]
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4.	J Antimicrob Chemother. 2010 Oct 18. [Epub ahead of print] Mechanism of interaction of sitamaquine with Leishmania donovani. Coimbra ES, Libong D, Cojean S, Saint-Pierre-Chazalet M, Solgadi A, Le Moyec L, Duenas-Romero AM, Chaminade P, Loiseau PM. Univ Paris-Sud, UMR 8076, Chimiothérapie Antiparasitaire, Faculté de Pharmacie, 5 rue Jean-Baptiste Clément, Chatenay-Malabry, F-92296, France. Abstract Objectives This study focuses on the mechanism of interaction of sitamaquine with Leishmania donovani membranes, and its accumulation within the parasites. Methods A biomimetic model of the outer layer of a Leishmania plasma membrane was used to examine the interactions of sitamaquine with lipids. The plasma membranes of L. donovani promastigotes were depleted of sterol using cholesterol oxidase, in order to assess the importance of sterols in drug-membrane interactions. Sterols were quantified and sitamaquine susceptibility was assessed using the MTT test. Kinetics of sitamaquine accumulation and efflux were measured under different conditions. Results Sitamaquine interacts first with phospholipid anionic polar head groups and then with phospholipid acyl chains to insert within biological membranes and accumulates rapidly in the Leishmania cytosol according to a sterol-independent process. The rapid sitamaquine efflux observed was related to an energy-dependent mechanism since the intracellular amount of sitamaquine was enhanced three times in the absence of glucose and the efflux was inhibited in energy-depleted conditions. (1)H NMR analysis of motile lipid showed that sitamaquine did not affect lipid trafficking in Leishmania. Conclusions We propose that sitamaquine rapidly accumulates in Leishmania by diffusion along an electrical gradient and is concentrated in the cytosol by an energy- and sterol-independent process. The affinity of sitamaquine for membranes was transitory and an energy-dependent efflux was demonstrated, suggesting the presence of an as yet uncharacterized transporter.
	PMID: 20956354 [PubMed - as supplied by publisher]
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5.	Exp Dermatol. 2010 Oct 18. doi: 10.1111/j.1600-0625.2010.01172.x. [Epub ahead of print] IL-1 signalling is dispensable for protective immunity in Leishmania-resistant mice. Kautz-Neu K, Kostka SL, Dinges S, Iwakura Y, Udey MC, Von Stebut E. Department of Dermatology, Johannes-Gutenberg University, Mainz, Germany Center for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, Tokyo, Japan Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agnecy, Saitama, Japan Dermatology Branch, NCI, NIH, Bethesda, MD, USA. Abstract   Leishmaniasis is a parasitic disease affecting ∼12 million people. Control of infection (e.g. in C57BL/6 mice) results from IL-12-dependent production of IFNγ by Th1/Tc1 cells. In contrast, BALB/c mice succumb to infection because of preferential Th2-type cytokine induction. Infected dendritic cells (DC) represent important sources of IL-12. Genetically determined differences in DC IL-1α/β production contribute to disease outcome. Whereas the course of disease was not dramatically altered in IL-1RI(-/-) mice, local administration of IL-1α to infected C57BL/6 mice improved disease outcome. To definitively elucidate the involvement of IL-1 in immunity against leishmaniasis, we now utilized IL-1α/β-double-deficient C57BL/6 mice. C57BL/6 mice are believed to be a good surrogate model for human, self limited cutaneous leishmaniasis (CL). Leishmania major-infected IL-1α/β(-/-) mice were resistant to experimental CL comparable to controls. In addition, DC-based vaccination against leishmaniasis in C57BL/6 mice was independent of IL-1. Thus, in Leishmania-resistant C57BL/6 mice, IL-1 signalling is dispensable for protection. © 2010 John Wiley & Sons A/S.
	PMID: 20955202 [PubMed - as supplied by publisher]
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6.	Protein Pept Lett. 2010 Oct 18. [Epub ahead of print] Intracellular Protozoan Parasites of Humans: The Role of Molecular Chaperones in Development and Pathogenesis. Shonhai A, Maier AG, Przyborski JM, Blatch GL. Department of Biochemistry & Microbiology, University of Zululand, Kwadlangezwa, South Africa. G.Blatch@ru.ac.za. Abstract Certain kinetoplastid (Leishmania spp. and Tryapnosoma cruzi) and apicomplexan parasites (Plasmodium falciparum and Toxoplasma gondii) are capable of invading human cells as part of their pathology. These parasites appear to have evolved a relatively expanded or diverse complement of genes encoding molecular chaperones. The gene families encoding heat shock protein 90 (Hsp90) and heat shock protein 70 (Hsp70) chaperones show significant expansion and diversity (especially for Leishmania spp. and T. cruzi), and in particular the Hsp40 family appears to be an extreme example of phylogenetic radiation. In general, Hsp40 proteins act as co-chaperones of Hsp70 chaperones, forming protein folding pathways that integrate with Hsp90 to ensure proteostasis in the cell. It is tempting to speculate that the diverse environmental insults that these parasites endure have resulted in the evolutionary selection of a diverse and expanded chaperone network. Hsp90 is involved in development and growth of all of these intracellular parasites, and so far represents the strongest candidate as a target for chemotherapeutic interventions. While there have been some excellent studies on the molecular and cell biology of Hsp70 proteins, relatively little is known about the biological function of Hsp70-Hsp40 interactions in these intracellular parasites. This review focuses on intracellular protozoan parasites of humans, and provides a critique of the role of heat shock proteins in development and pathogenesis, especially the molecular chaperones Hsp90, Hsp70 and Hsp40.
	PMID: 20955165 [PubMed - as supplied by publisher]
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7.	Vector Borne Zoonotic Dis. 2010 Oct 18. [Epub ahead of print] Natural Infections of Man-Biting Sand Flies by Leishmania and Trypanosoma Species in the Northern Peruvian Andes. Kato H, Gomez EA, Cáceres AG, Vargas F, Mimori T, Yamamoto K, Iwata H, Korenaga M, Velez L, Hashiguchi Y. 1 Laboratory of Veterinary Hygiene, Faculty of Agriculture, Yamaguchi University , Yamaguchi, Japan . Abstract Abstract The natural infection of sand flies by Leishmania species was studied in the Andean areas of Peru where cutaneous leishmaniasis caused by Leishmania (Viannia) peruviana is endemic. Sand flies were captured by human bait and Center for Disease Control (CDC) light trap catches at Nambuque and Padregual, Department of La Libertad, Peru, and morphologically identified. Among 377 female sand flies dissected, the two dominant man-biting species were Lutzomyia (Helcocyrtomyia) peruensis (211 flies) and Lutzomyia (Helcocyrtomyia) caballeroi (151 flies). Another sand fly species captured by light trap was Warileya phlebotomanica (15 flies). The natural infection of sand flies by flagellates was detected in 1.4% of Lu. (H.) peruensis and 2.6% of Lu. (H.) caballeroi, and the parasite species were identified as Le. (V.) peruviana and Trypanosoma avium, respectively, by molecular biological methods. The results indicated that the vector species responsible for the transmission of leishmaniasis in the study areas is Lu. (H.) peruensis. In addition, the presence of Trypanosoma in man-biting sand fly species means that more careful consideration is necessary for vector research in areas of Andean Peru where leishmaniasis is endemic.
	PMID: 20954867 [PubMed - as supplied by publisher]
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8.	J Nat Prod. 2010 Oct 18. [Epub ahead of print] Caffeic Acid Esters and Lignans from Piper sanguineispicum. Cabanillas BJ, Le Lamer AC, Castillo D, Arevalo J, Rojas R, Odonne G, Bourdy G, Moukarzel B, Sauvain M, Fabre N. Université de Toulouse, UPS, UMR 152 (Laboratoire de Pharmacochimie des Substances Naturelles et Pharmacophores Redox), F-31062 Toulouse Cedex 9, France, IRD, UMR-152, Mission IRD Casilla 18-1209 Lima, Perú, and Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Avenida Honorio Delgado 430, San Martin de Porres, Lima, Perú Abstract Three new caffeic acid esters (1-3), four new lignans (4-7), and the known compounds (7'S)-parabenzlactone (8), dihydrocubebin (9), and justiflorinol (10) have been isolated from leaves of Piper sanguineispicum. Their structures were determined by spectroscopic methods, including 1D and 2D NMR, HRCIMS, CD experiments, and chemical methods. Compounds 1-10 were assessed for their antileishmanial potential against axenic amastigote forms of Leishmania amazonensis. Caffeic acid esters 1 and 3 exhibited the best antileishmanial activity (IC(50) 2.0 and 1.8 μM, respectively) with moderate cytotoxicity on murine macrophages.
	PMID: 20954722 [PubMed - as supplied by publisher]
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9.	Diagn Microbiol Infect Dis. 2010 Aug;67(4):402-5. Comparison of the analytic sensitivities of a recombinant immunoblot assay and the radioimmune precipitation assay for the detection of antibodies to Trypanosoma cruzi in patients with Chagas disease. Shah DO, Chang CD, Cheng KY, Salbilla VA, Adya N, Marchlewicz BA, Kirchhoff LV. Emerging Pathogens and Infectious Diseases R&D, Abbott Diagnostics Division, Abbott Laboratories, IL 60064, USA. dinesh.shah@abbott.com Abstract The diagnosis of chronic Chagas disease usually is made by detecting antibodies to Trypanosoma cruzi, the protozoan parasite that causes this illness. A highly sensitive and specific immunoblot assay developed by us showed a higher analytic sensitivity than the radioimmune precipitation assay, which is used widely as a confirmatory test. Copyright 2010 Elsevier Inc. All rights reserved.
	PMID: 20638614 [PubMed - indexed for MEDLINE]
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10.	Mol Biochem Parasitol. 2010 Oct;173(2):132-41. Epub 2010 Jun 2. Identification, cloning and characterization of an aldo-keto reductase from Trypanosoma cruzi with quinone oxido-reductase activity. Garavaglia PA, Cannata JJ, Ruiz AM, Maugeri D, Duran R, Galleano M, García GA. Instituto Nacional de Parasitología Dr. Mario Fatala Chaben-A.N.L.I.S. Dr. Carlos G. Malbrán, Buenos Aires 1063, Argentina. gaandgarcia@yahoo.com Abstract Drugs currently used for treatment of Trypanosoma cruzi infection, the ethiological agent of Chagas' disease, have shown side effects and variable efficiency. With the aim to describe parasite enzymes involved in the mechanisms of action of trypanocidal drugs and since it has been reported that reductases are crucial in their metabolism, we attempted to identify novel NADPH-dependent oxido-reductases from T. cruzi. The percolation of a soluble fraction of epimastigote lysates through a Cibacron Blue-Sepharose column followed by elution by NADPH yielded a predominant protein with an apparent molecular weight of 32 kDa. This protein was identified by MALDI-TOF as an aldo-keto reductase (AKR) and hence denominated TcAKR. TcAKR was mainly localized in the cytosol and was also present in trypomastigote and amastigote lysates. The recombinant TcAKR (recTcAKR) showed NADPH-dependent reductase activity with the AKR substrates 4-nitrobenzaldehyde and 2-dihydroxyacetone. The saturation curves for both substrates were consistent with the Michaelis-Menten model. We also tested whether recTcAKR may reduce naphthoquinones (NQ), since many of these compounds have displayed important trypanocidal activity. recTcAKR reduced o-NQ (1,2-naphthoquinone, 9,10-phenanthrenquinone and beta-lapachone) with concomitant generation of free radicals but did not exhibit affinity for p-NQ (5-hydroxy-1,4-naphthoquinone, 2-hydroxy-1,4-naphthoquinone, alpha-lapachone and menadione). The substrate saturation curve with o-NQ fitted to a sigmoidal curve, suggesting that recTcAKR presents a cooperative behavior. In addition, three peaks assigned to monomers, dimers and tetramers were obtained when recTcAKR was submitted to a Superose 12 gel chromatography column. TcAKR is the first member of the AKR family described in T. cruzi. Our results indicate that this enzyme may participate in the mechanisms of action of trypanocidal drugs. Copyright 2010 Elsevier B.V. All rights reserved.
	PMID: 20595031 [PubMed - indexed for MEDLINE]
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