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Sent on Tuesday, 2012 January 31Search: kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | Virulence. 2012 Jan 1;3(1). [Epub ahead of print]Haptoglobin-hemoglobin receptor independent killing of African trypanosomes by human serum.Bullard W, Kieft R, Capewell P, Veitch NJ, Macleod A, Hajduk S.SourceDepartment of Biochemistry and Molecular Biology; University of Georgia; Athens, GA USA. AbstractThe haptoglobin-hemoglobin receptor (HpHbR) of African trypanosomes plays a critical role in human innate immunity against these parasites. Localized to the flagellar pocket of the veterinary pathogen Trypanosoma brucei brucei this receptor binds Trypanosome Lytic Factor-1 (TLF-1), a subclass of human high-density lipoprotein (HDL) facilitating endocytosis, lysosomal trafficking and subsequent killing. Recently, we found that group 1 Trypanosoma brucei gambiense does not express a functional HpHbR. We now show that loss of the TbbHpHbR reduces the susceptibility of T. b. brucei to human serum and TLF-1 by 100- and 10,000-fold respectively. The relatively high concentrations of human serum and TLF-1 needed to kill trypanosomes lacking the HpHbR indicates that high affinity TbbHpHbR binding enhances the cytotoxicity; however in the absence of TbbHpHbR other receptors or fluid phase endocytosis are sufficient to provide some level of susceptibility. Human serum contains a second innate immune factor, TLF-2, that has been suggested to kill trypanosomes independently of the TbbHpHbR. We found that T. b. brucei killing by TLF-2 was reduced in TbbHpHbR deficient cells but to a lesser extent than TLF-1. This suggests that both TLF-1 and TLF-2 can be taken up via the TbbHpHbR but that alternative pathways exist for the uptake of these toxins. Together the findings reported here extend our previously published studies and suggest that group 1 T. b. gambiense has evolved multiple mechanisms to avoid killing by trypanolytic human serum factors. |
| 2. | Rev Chilena Infectol. 2011 Dec;28(6):520-8. Epub 2012 Jan 5.[Travellers to South america]. [Article in Spanish] Lloveras SC.SourceÁrea de Medicina del Viajero, Centro Municipal de Patologías Regionales Argentinas y Medicina Tropical, Hospital F. J. Muñiz, Buenos Aires, Argentina. AbstractThe geography, tourist attractions and the multiple sites of historical and cultural interest make South America as an important destination chosen by travelers. The continent has a wide climatic variation from north to south, making exposure to risk different between the tropics and the temperate or cold regions. In the countries of tropical South America, the greatest risk is associated with the possibility of acquiring vector-borne diseases, like yellow fever, dengue, malaria and leishmaniasis. The risk of acquiring traveler's diarrhea and food-borne illness is similar across the continent, with some variations according to country and to visit urban or rural areas. Rabies, pertussis and diphtheria have appeared as epidemics in several countries and other diseases such as rickettsiosis, hantavirosis and viral encephalitis have expanded their distribution. The geographic and epidemiological diversity of South America, promotes a challenge for travel medicine specialists because during the pre-travel advice they have to take in account the kind of trip, traveller's medical history, exposure to risk and the dynamics of endemic emerging and reemerging diseases in the region. |
| 3. | Nat Methods. 2012 Jan 29. doi: 10.1038/nmeth.1859. [Epub ahead of print]In vivo protein crystallization opens new routes in structural biology.Koopmann R, Cupelli K, Redecke L, Nass K, Deponte DP, White TA, Stellato F, Rehders D, Liang M, Andreasson J, Aquila A, Bajt S, Barthelmess M, Barty A, Bogan MJ, Bostedt C, Boutet S, Bozek JD, Caleman C, Coppola N, Davidsson J, Doak RB, Ekeberg T, Epp SW, Erk B, Fleckenstein H, Foucar L, Graafsma H, Gumprecht L, Hajdu J, Hampton CY, Hartmann A, Hartmann R, Hauser G, Hirsemann H, Holl P, Hunter MS, Kassemeyer S, Kirian RA, Lomb L, Maia FR, Kimmel N, Martin AV, Messerschmidt M, Reich C, Rolles D, Rudek B, Rudenko A, Schlichting I, Schulz J, Seibert MM, Shoeman RL, Sierra RG, Soltau H, Stern S, Strüder L, Timneanu N, Ullrich J, Wang X, Weidenspointner G, Weierstall U, Williams GJ, Wunderer CB, Fromme P, Spence JC, Stehle T, Chapman HN, Betzel C, Duszenko M.Source1] Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany. [2]. AbstractProtein crystallization in cells has been observed several times in nature. However, owing to their small size these crystals have not yet been used for X-ray crystallographic analysis. We prepared nano-sized in vivo-grown crystals of Trypanosoma brucei enzymes and applied the emerging method of free-electron laser-based serial femtosecond crystallography to record interpretable diffraction data. This combined approach will open new opportunities in structural systems biology. |
| 4. | Eukaryot Cell. 2012 Jan 27. [Epub ahead of print]Dynamic localization of Trypanosoma brucei mitochondrial DNA polymerase ID.Concepción-Acevedo J, Luo J, Klingbeil MM.SourceDepartment of Microbiology, University of Massachusetts, Amherst, Massachusetts 01003. AbstractTrypanosomes contain a unique form of mitochondrial DNA called kinetoplast DNA (kDNA) that is a catenated network composed of minicircles and maxicircles. Several proteins are essential for network replication and most of these localize to the antipodal sites or the kinetoflagellar zone. Essential components for kDNA synthesis include three mitochondrial DNA polymerases (TbPOLIB, IC, ID). In contrast to other kDNA replication proteins, TbPOLID was previously reported to localize throughout the mitochondrial matrix. This spatial distribution suggests that TbPOLID would require redistribution to engage in kDNA replication. Here we characterize the subcellular distribution of TbPOLID with respect to the Trypanosoma brucei cell cycle using immunofluorescence microscopy. Our analyses demonstrate that in addition to the previously reported matrix localization, TbPOLID was detected as discrete foci near the kDNA. TbPOLID foci colocalized with replicating minicircles at antipodal sites in a specific subset of the cells during stage II-III of kDNA replication. Additionally, the TbPOLID foci were stable following inhibition of protein synthesis, detergent extraction and DNase treatment. Together, these data demonstrate that TbPOLID has a dynamic localization that allows it to be spatially and temporally available to perform its role in kDNA replication. |
| 5. | Phytomedicine. 2012 Jan 27. [Epub ahead of print]Effects of (-) mammea A/BB isolated from Calophyllum brasiliense leaves and derivatives on mitochondrial membrane of Leishmania amazonensis.Brenzan MA, Santos AO, Nakamura CV, Filho BP, Ueda-Nakamura T, Young MC, Côrrea AG, Júnior JA, Morgado-Díaz JA, Cortez DA.SourcePós-doutoranda em Ciências Farmacêuticas, Departamento de Farmácia e Farmacologia, Universidade Estadual de Maringá, Av. Colombo 5790, 87020-900 Maringá, PR, Brazil. AbstractWe have previously demonstrated antileishmanial activity on Leishmania amazonensis of the natural (1-2), synthetic (7) and derivatives of coumarin (-) mammea A/BB (3-6) isolated from the dichloromethane extract of Calophyllum brasiliense leaves. The aim of the present study was to evaluate morphological and ultrastructural alterations in Leishmania amazonensis induced by these compounds. In promastigote forms, all seven compounds produced significant morphological and ultrastructural alterations, as revealed by scanning and transmission electron microscopy. The compound 5,7-dihydroxy-8-(2-methylbutanoyl)-6-(3-methylbutyl)-4-phenyl-chroman-2-one (3), the most active antileishmanial with LD(50) of 0.9μM), induced cell shrinkage and a rounded appearance of the cells. Parasites incubated in the presence of compound (3) showed ultrastructural changes, such as the appearance of mitochondrial swelling with a reduction in the density of the mitochondrial matrix and the presence of vesicles inside the mitochondrion, indicating damage and significant change in this organelle; abnormal chromatin condensation, alterations in the nuclear envelope, intense atypical cytoplasmic vacuolization, and the appearance of autophagic vacuoles were also observed. In addition, the compound (3) may be acting to depolarize the mitochondrial membrane potential of the cells, leading to death of the parasite. Copyright © 2011 Elsevier GmbH. All rights reserved. |
| 6. | J Struct Biol. 2012 Jan 25. [Epub ahead of print]Cryo-electron tomography and 3-D analysis of the intact flagellum in Trypanosoma brucei.Höög JL, Bouchet-Marquis C, McIntosh RJ, Hoenger A, Gull K.SourceThe Boulder Laboratory for 3-D Electron Microscopy of Cells, MCD-Biology, University of Colorado at Boulder, Boulder, CO 80309-0347, USA; The Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK. AbstractTrypanosoma brucei is a uni-cellular protist that causes African sleeping sickness. These parasites have a flagellum that is attached to the cell body and is indispensible for its motility. The flagellum consists of a canonical 9+2 axoneme and a paraflagellar rod (PFR), an intricate tripartite, fibrous structure that is connected to the axoneme. In this paper we describe results from cryo-electron tomography of unperturbed flagella. This method revealed novel structures that are likely involved in attaching the flagellum to the cell. We also show the first cryo-electron tomographic images of a basal body in situ, revealing electron dense structures inside its triplet microtubules. Sub-tomogram averaging of the PFR revealed that its distal region is organized as an orthorhombic crystal. Copyright © 2012 Elsevier Inc. All rights reserved. |
| 7. | Infect Genet Evol. 2012 Jan 21. [Epub ahead of print]Multiple infections of Trypanosoma brucei gambiense in blood and cerebrospinal fluid of human African trypanosomosis patients from Angola: Consequences on clinical course and treatment outcome.Truc P, Tiouchichine ML, Cuny G, Vatunga G, Josenando T, Simo G, Herder S.SourceInstitut de Recherche pour le Développement, Unité Mixte de Recherche 177 IRD-CIRAD, Campus International de Baillarguet, TA A17/G, 34398 Montpellier Cedex 5, France. AbstractHuman African trypanosomosis, caused by Trypanosoma brucei gambiense, is a chronic disease, although various clinical patterns have been observed, from asymptomatic to acute forms. Since 2001 in Angola, 80% of patients have been found to be in the meningoencephalitic stage of the disease. The existence of an acute form of the disease caused by virulent strains of trypanosomes was suspected. To test this hypothesis, four sensitive and polymorphic microsatellite markers were used to characterize the trypanosome DNA extracted from the blood and cerebrospinal fluid of 100 patients in the meningoencephalitic stage. Twenty-three patients were found with mixed T. b. gambiense genotypes in the blood and/or cerebrospinal fluid. The absence of association between the number of infecting genotypes, the presence of neurological signs and white blood cell counts in the cerebrospinal fluid, seems to indicate, at least in the context of the present study, the absence of virulent strains. However, out of five patients who died from encephalopathy syndrome during treatment with eflornithine, three harbored multiple infections. Copyright © 2012. Published by Elsevier B.V. |
| 8. | Bioorg Med Chem. 2012 Jan 2. [Epub ahead of print]Synthesis and antimalarial and antituberculosis activities of a series of natural and unnatural 4-methoxy-6-styryl-pyran-2-ones, dihydro analogues and photo-dimers.McCracken ST, Kaiser M, Boshoff HI, Boyd PD, Copp BR.SourceSchool of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand. AbstractPrevious studies have identified the 3,6-dialkyl-4-hydroxy-pyran-2-one marine microbial metabolites pseudopyronines A and B to be modest growth inhibitors of Mycobacterium tuberculosis and a range of tropical diseases including Plasmodium falciparum and Leishmania donovani. In an effort to expand the structure-activity relationship of this compound class towards infectious diseases, a library of natural product and natural product-like 4-methoxy-6-styryl-pyran-2-ones and a subset of catalytically reduced examples were synthesized. In addition, the photochemical reactivity of several of the 4-methoxy-6-styryl-pyran-2-ones were investigated yielding head-to-head and head-to-tail cyclobutane dimers as well as examples of asymmetric aniba-dimer A-type dimers. All compounds were evaluated for cytotoxicity and activity against M. tuberculosis, P. falciparum, L. donovani, Trypanosoma brucei rhodesiense and Trypanosoma cruzi. Of the styryl-pyranones, natural product 3 and non-natural styrene and naphthalene substituted examples 13, 18, 21, 22 and 23 exhibited antimalarial activity (IC(50) <10μM) with selectivity indices (SI) >10. Δ(7) Dihydro analogues were typically less active or lacked selectivity. Head-to-head and head-to-tail photodimers 5 and 34 exhibited moderate IC(50)s of 2.3 to 17μM towards several of the parasitic organisms, while the aniba-dimer-type asymmetric dimers 31 and 33 were identified as being moderately active towards P. falciparum (IC(50) 1.5 and 1.7μM) with good selectivity (SI ∼80). The 4-tert-butyl aniba-dimer A analogue 33 also exhibited activity towards L. donovani (IC(50) 4.5μM), suggesting further elaboration of this latter scaffold could lead to the identification of new leads for the dual treatment of malaria and leishmaniasis. Copyright © 2011 Elsevier Ltd. All rights reserved. |
| 9. | Vet Parasitol. 2012 Jan 10. [Epub ahead of print]Coinfection of Leishmania chagasi with Toxoplasma gondii, Feline Immunodeficiency Virus (FIV) and Feline Leukemia Virus (FeLV) in cats from an endemic area of zoonotic visceral leishmaniasis.Sobrinho LS, Rossi CN, Vides JP, Braga ET, Gomes AA, de Lima VM, Perri SH, Generoso D, Langoni H, Leutenegger C, Biondo AW, Laurenti MD, Marcondes M.SourceDepartment of Clinics, Surgery and Animal Reproduction, College of Veterinary Medicine, São Paulo State University, Araçatuba, São Paulo 16050-680, Brazil. AbstractThe aim of the present study was to determine the coinfection of Leishmania sp. with Toxoplasma gondii, Feline Immunodeficiency Virus (FIV) and Feline Leukemia Virus (FeLV) in a population of cats from an endemic area for zoonotic visceral leishmaniasis. An overall 66/302 (21.85%) cats were found positive for Leishmania sp., with infection determined by direct parasitological examination in 30/302 (9.93%), by serology in 46/302 (15.23%) and by both in 10/302 (3.31%) cats. Real time PCR followed by amplicon sequencing successfully confirmed Leishmania infantum (syn Leishmania chagasi) infection. Out of the Leishmania infected cats, coinfection with FIV was observed in 12/66 (18.18%), with T. gondii in 17/66 (25.75%) and with both agents in 5/66 (7.58%) cats. FeLV was found only in a single adult cat with no Leishmania infection. A positive association was observed in coinfection of Leishmania and FIV (p<0.0001), but not with T. gondii (p>0.05). In conclusion, cats living in endemic areas of visceral leishmaniasis are significantly more likely to be coinfected with FIV, which may present confounding clinical signs and therefore cats in such areas should be always carefully screened for coinfections. Copyright © 2012 Elsevier B.V. All rights reserved. |
| 10. | Trans R Soc Trop Med Hyg. 2012 Jan 25. [Epub ahead of print]Risk factors for cutaneous leishmaniasis in Cukurova region, Turkey.Votýpka J, Kasap OE, Volf P, Kodym P, Alten B.SourceDepartment of Parasitology, Charles University, Vinicna 7, Prague 128 44, Czech Republic. AbstractWe conducted a case-control study to evaluate risk factors for cutaneous leishmaniasis caused by Leishmania infantum outbreaks in villages in the Cukurova region, South Anatolia, Turkey. 282 respondents from eight villages were interviewed using structured questionnaires. Epidemiological and clinical characteristics, personal protection and knowledge of leishmania were analyzed. Young people, aged from 5-19 years, were found to be the most endangered group of villagers. The concurrent presence of both lesions and scars in nine persons may indicate repeated infections. Sleeping without bed nets, ownership of a dog and cattle ownership (living close to a barn and storage of dried dung according univariate analyses) were associated with a significantly increased risk of leishmania infection. Non-impregnated bed nets provided only partial protection, but their use decreased the risk approximately 1.6 times. Further research on the role of dogs in the transmission cycle and the effect of suitable interventions are needed to design the best strategy for disease control. Results suggest that personal protection should be increased, particularly among outdoor sleepers, with insecticide-treated bed nets suggested as the best choice. Copyright © 2011 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved. |
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