What's new for 'Trypanosomatids' in PubMed

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Sent on Saturday, 2012 June 09
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 - 7 of 7

1.	PLoS Negl Trop Dis. 2012 Jun;6(6):e1668. Epub 2012 Jun 5. Isothermal Microcalorimetry, a New Tool to Monitor Drug Action against Trypanosoma brucei and Plasmodium falciparum. Wenzler T, Steinhuber A, Wittlin S, Scheurer C, Brun R, Trampuz A. Source Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland. Abstract Isothermal microcalorimetry is an established tool to measure heat flow of physical, chemical or biological processes. The metabolism of viable cells produces heat, and if sufficient cells are present, their heat production can be assessed by this method. In this study, we investigated the heat flow of two medically important protozoans, Trypanosoma brucei rhodesiense and Plasmodium falciparum. Heat flow signals obtained for these pathogens allowed us to monitor parasite growth on a real-time basis as the signals correlated with the number of viable cells. To showcase the potential of microcalorimetry for measuring drug action on pathogenic organisms, we tested the method with three antitrypanosomal drugs, melarsoprol, suramin and pentamidine and three antiplasmodial drugs, chloroquine, artemether and dihydroartemisinin, each at two concentrations on the respective parasite. With the real time measurement, inhibition was observed immediately by a reduced heat flow compared to that in untreated control samples. The onset of drug action, the degree of inhibition and the time to death of the parasite culture could conveniently be monitored over several days. Microcalorimetry is a valuable element to be added to the toolbox for drug discovery for protozoal diseases such as human African trypanosomiasis and malaria. The method could probably be adapted to other protozoan parasites, especially those growing extracellularly.
	PMID: 22679520 [PubMed - in process]

2.	PLoS Negl Trop Dis. 2012 Jun;6(6):e1667. Epub 2012 Jun 5. Genetics of Host Response to Leishmania tropica in Mice - Different Control of Skin Pathology, Chemokine Reaction, and Invasion into Spleen and Liver. Kobets T, Havelková H, Grekov I, Volkova V, Vojtíšková J, Slapničková M, Kurey I, Sohrabi Y, Svobodová M, Demant P, Lipoldová M. Source Laboratory of Molecular and Cellular Immunology, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic. Abstract BACKGROUND: Leishmaniasis is a disease caused by protozoan parasites of genus Leishmania. The frequent involvement of Leishmania tropica in human leishmaniasis has been recognized only recently. Similarly as L. major, L. tropica causes cutaneous leishmaniasis in humans, but can also visceralize and cause systemic illness. The relationship between the host genotype and disease manifestations is poorly understood because there were no suitable animal models. METHODS: We studied susceptibility to L. tropica, using BALB/c-c-STS/A (CcS/Dem) recombinant congenic (RC) strains, which differ greatly in susceptibility to L. major. Mice were infected with L. tropica and skin lesions, cytokine and chemokine levels in serum, and parasite numbers in organs were measured. PRINCIPAL FINDINGS: Females of BALB/c and several RC strains developed skin lesions. In some strains parasites visceralized and were detected in spleen and liver. Importantly, the strain distribution pattern of symptoms caused by L. tropica was different from that observed after L. major infection. Moreover, sex differently influenced infection with L. tropica and L. major. L. major-infected males exhibited either higher or similar skin pathology as females, whereas L. tropica-infected females were more susceptible than males. The majority of L. tropica-infected strains exhibited increased levels of chemokines CCL2, CCL3 and CCL5. CcS-16 females, which developed the largest lesions, exhibited a unique systemic chemokine reaction, characterized by additional transient early peaks of CCL3 and CCL5, which were not present in CcS-16 males nor in any other strain. CONCLUSION: Comparison of L. tropica and L. major infections indicates that the strain patterns of response are species-specific, with different sex effects and largely different host susceptibility genes.
	PMID: 22679519 [PubMed - in process]

3.	Bioorg Med Chem Lett. 2012 May 17. [Epub ahead of print] Iotrochamides A and B, antitrypanosomal compounds from the Australian marine sponge Iotrochota sp. Feng Y, Davis RA, Sykes ML, Avery VM, Quinn RJ. Source Eskitis Institute, Griffith University, Brisbane, QLD 4111, Australia. Abstract Bioassay-guided isolation of the CH(2)Cl(2)/MeOH extract from the Australian sponge Iotrochota sp. resulted in the purification of two new N-cinnamoyl-amino acids, iotrochamides A (1) and B (2). The chemical structures of 1 and 2 were determined by 1D/2D NMR and MS data analyses. Compounds 1 and 2 were shown to inhibit Trypanosoma brucei brucei with IC(50) values of 3.4 and 4.7μM, respectively. Copyright © 2012 Elsevier Ltd. All rights reserved.
	PMID: 22677313 [PubMed - as supplied by publisher]

4.	Vet Parasitol. 2012 May 23. [Epub ahead of print] The hare (Lepus granatensis) as potential sylvatic reservoir of Leishmania infantum in Spain. Molina R, Jiménez MI, Cruz I, Iriso A, Martín-Martín I, Sevillano O, Melero S, Bernal J. Source Servicio de Parasitología, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Ctra. Majadahonda-Pozuelo s/n, 28220 Majadahonda, Madrid, Spain. Abstract Xenodiagnosis of Leishmania infection in hares (Lepus granatensis) from a focus of human leishmaniasis in Fuenlabrada at southwestern Madrid region (Spain) proved that they are infective to Phlebotomus perniciosus. Molecular characterization of isolates obtained from sand flies infected after xenodiagnosis demonstrates that hares were infected by Leishmania infantum. This is the first evidence of the transmission of L. infantum from hares to sand flies. Moreover the results confirm the role that these animals can play as wild reservoirs of leishmaniasis for the recent outbreak of visceral leishmaniasis in Madrid. Copyright © 2012 Elsevier B.V. All rights reserved.
	PMID: 22677135 [PubMed - as supplied by publisher]

5.	Mol Microbiol. 2012 Jun 7. doi: 10.1111/j.1365-2958.2012.08124.x. [Epub ahead of print] Phosphoglucomutase is absent in Trypanosoma brucei and redundantly substituted by phosphomannomutase and phospho-N-acetylglucosamine mutase. Bandini G, Mariño K, Güther ML, Wernimont AK, Kuettel S, Qiu W, Afzal S, Kelner A, Hui R, Ferguson MA. Source Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, United Kingdom. Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada. Abstract The enzymes phosphomannomutase (PMM), phospho-N-acetylglucosamine mutase (PAGM) and phosphoglucomutase (PGM) reversibly catalyze the transfer of phosphate between the C6 and C1 hydroxyl groups of mannose, N-acetylglucosamine and glucose, respectively. Although genes for a candidate phosphomannomutase and a phospho-N-acetylglucosamine mutase enzymes have been found in the Trypanosoma brucei genome there is, surprisingly, no candidate gene for phosphoglucomutase. The TbPMM and TbPAGM genes were cloned and expressed in Escherichia coli and the TbPMM enzyme was crystallized and its structure solved at 1.85Å resolution. Antibodies to the recombinant proteins localized endogenous TbPMM to glycosomes in the bloodstream form of the parasite while TbPAGM localized to both the cytosol and glycosomes. Both recombinant enzymes were able to interconvert glucose-phosphates, as well as acting on their own definitive substrates. Analysis of sugar nucleotide levels in parasites with TbPMM or TbPAGM knocked down by RNA interference (RNAi) suggests that, in vivo, PGM activity is catalyzed by both enzymes. This is the first example in any organism of PGM activity being completely replaced in this way and it explains why, uniquely, T. brucei has been able to lose its PGM gene. The RNAi data for TbPMM also showed that this is an essential gene for parasite growth. © 2012 Blackwell Publishing Ltd. © 2012 Blackwell Publishing Ltd.
	PMID: 22676716 [PubMed - as supplied by publisher]

6.	Parasit Vectors. 2012 Jun 7;5(1):111. [Epub ahead of print] Natural infection of Didelphis aurita (Mammalia: Marsupialia) with Leishmania infantum in Brazil. Carreira JC, Machado da Silva AV, Pereira DD, Brazil RP. Abstract ABSTRACT: BACKGROUND: The opossum Didelphis have been considered as natural hosts of Leishmania parasites in the New World, suggesting an important role in the epidemiology of Visceral Leishmaniasis (VL). Among six extant species that belong to the genus Didelphis, only two (D. marsupialis and D. albiventris), have been mentioned as natural hosts of Leishmania infantum in Brazil and Colombia. In the present paper, it is reported for the first time, the observation of intracellular parasites (amastigotes) in tissues of Didelphis aurita naturally infected with Leishmania infantum in Brazil. We also discuss some aspects associated to the relationship between L. infantum and the geographical distribution of some species of the genus Didelphis. METHODS: The opossums studied were caught by wire traps (Tomahawk) in Barra de Guaratiba, a peri-urban area in Rio de Janeiro. The opossums were killed with an overdose of Thiopental sodium.At necropsy, macroscopic alterations were examined and samples from liver, spleen, lymph nodes, ear, abdominal skin, scent glands and bone marrow were collected for parasitological and molecular diagnoses. RESULTS: Forty-eight opossums were captured in an AVL endemic region, 30 being caught in a mangrove area and eighteen animals in a forest area near to some residential-yards. Among the thirty opossums trapped in the mangrove area, all of them were negative by both imprint and sera samples assayed on Dipstick Tests, that is a test based on a combination of protein-A colloidal gold conjugate and rk39 Leishmania antigen to detect anti-Leishmania antibody in serum or plasma. At the macroscopic examination one out of eighteen opossums, caught close to the forest, presented alterations compatible with spleen hypertrophy and three were positive by Dipstick Tests (16.6%) and presented amastigotes in the spleen and in one of them, the parasites were also observed in a submandibular lymph node. Leishmania infantum infections were confirmed through dot blot hybridization using a L. infantum-specific biotinylated probe. CONCLUSIONS: In the present paper we present the first report of amastigotes in the tissues of Didelphis aurita (Mammalia: Marsupialia) naturally infected with Leishmania infantum. We also attempt to claim the particular role of some opossum species as hosts of Leishmania infantum, contributing at least in part on the description of potential sylvatic reservoirs.
	PMID: 22676324 [PubMed - as supplied by publisher]

7.	Parasit Vectors. 2012 Jun 7;5(1):109. [Epub ahead of print] The life cycle of Trypanosoma (Nannomonas) congolense in the tsetse fly. Peacock L, Cook S, Ferris V, Bailey M, Gibson W. Abstract ABSTRACT: BACKGROUND: The tsetse-transmitted African trypanosomes cause diseases of importance to the health of both humans and livestock. The life cycles of these trypanosomes in the fly were described in the last century, but comparatively few details are available for Trypanosoma (Nannomonas) congolense, despite the fact that it is probably the most prevalent and widespread pathogenic species for livestock in tropical Africa. When the fly takes up bloodstream form trypanosomes, the initial establishment of midgut infection and invasion of the proventriculus is much the same in T. congolense and T. brucei. However, the developmental pathways subsequently diverge, with production of infective metacyclics in the proboscis for T. congolense and in the salivary glands for T. brucei. Whereas events during migration from the proventriculus are understood for T. brucei, knowledge of the corresponding developmental pathway in T. congolense is rudimentary. The recent publication of the genome sequence makes it timely to re-investigate the life cycle of T. congolense. METHODS: Experimental tsetse flies were fed an initial bloodmeal containing T. congolense strain 1/148 and dissected 2 to 78 days later. Trypanosomes recovered from the midgut, proventriculus, proboscis and cibarium were fixed and stained for digital image analysis. Trypanosomes contained in spit samples from individually caged flies were analysed similarly. Mensural data from individual trypanosomes were subjected to principal components analysis. RESULTS: Flies were more susceptible to infection with T. congolense than T. brucei; a high proportion of flies infected with T. congolense established a midgut and subsequent proboscis infection, whereas many T. brucei infections were lost in the migration from foregut to salivary glands. In T. congolense, trypomastigotes ceased division in the proventriculus and became uniform in size. The trypanosomes retained trypomastigote morphology during migration via the foregut to the mouthparts and we confirmed that the trypomastigote-epimastigote transition occurred in the proboscis. We found no equivalent to the asymmetric division stage in T. brucei that mediates transition of proventricular trypomastigotes to epimastigotes. In T. congolense extremely long epimastigotes with remarkably elongated posterior ends were observed in both the proboscis and cibarium; no difference was found in the developmental stages in these two organs. Dividing trypomastigotes and epimastigotes were recovered from the proboscis, some of which were in transition from trypomastigote to epimastigote and vice versa. It remains uncertain whether these morphological transitions are mediated by cell division, since we also found non-dividing cells with a variously positioned, juxta-nuclear kinetoplast. CONCLUSIONS: We have presented a detailed description of the life cycle of T. congolense in its tsetse fly vector. During development in the fly T. congolense shares a common migratory pathway with its close relative T. brucei, culminating in the production of small metacyclic trypanosomes that can be inoculated with the saliva. Despite this outward similarity in life cycle, the transitional developmental stages in the foregut and mouthparts are remarkably different in the two trypanosome species.
	PMID: 22676292 [PubMed - as supplied by publisher]