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Sent on Thursday, 2011 May 12Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | PLoS One. 2011 Apr 29;6(4):e19118.Intracellular eukaryotic parasites have a distinct unfolded protein response.Gosline SJ, Nascimento M, McCall LI, Zilberstein D, Thomas DY, Matlashewski G, Hallett M.SourceMcGill Centre for Bioinformatics, McGill University, Montréal, Québec, Canada. AbstractInsult to the endoplasmic reticulum (ER) activates the Unfolded Protein Response (UPR), a set of signaling pathways that protect the cell from the potential damage caused by improperly folded proteins. Accumulation of misfolded proteins in the ER lumen initiates a series of signal transduction events via activation of three transmembrane ER proteins: Ire1, Atf6 and PERK. Activation of these proteins results in the transcriptional up-regulation of the components of the folding, trafficking and degradation machinery in the ER. PERK further reduces the load on the ER via the phosphorylation of eIF2α, attenuating general protein translation. It is believed that the UPR evolved as a transcriptional response that up-regulates protein folding machinery in the ER and later gained the ability to decrease ER load by attenuating general protein translation in metazoa. However, our in silico analyses of protozoan parasites revealed an absence of proteins involved in the transcriptionally mediated UPR and the presence of both PERK and its target eIF2α. Consistent with these observations, stimulation of the UPR in Leishmania donovani identified an absence of up-regulation of the ER chaperone BiP, the canonical ER chaperone modulated by the UPR in higher eukaryotes, while exhibiting increased phosphorylation of eIF2α which has been shown to attenuate protein translation. We further observed that L. donovani is more sensitive to UPR inducing agents than host macrophages, suggesting that the less evolved stress response could provide a new avenue for therapeutic treatment of parasitic infections. |
| 2. | PLoS One. 2011 Apr 29;6(4):e19304.Diagnosis of Indian visceral leishmaniasis by nucleic Acid detection using PCR.Srivastava P, Mehrotra S, Tiwary P, Chakravarty J, Sundar S.SourceInfectious Disease Research Laboratory, Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. AbstractBACKGROUND:PCR based diagnosis for Visceral Leishmaniasis (VL), despite numerous published primers, remains far from being applied in the field. The present study was planned to design a Leishmania specific diagnostic assay and to evaluate its sensitivity and specificity on a sample size, which to the best of our knowledge is the largest ever screened in one study. METHODS:Leishmania specific primers were developed using 18S rRNA gene and their sensitivity was evaluated on 500 parasitologically confirmed patients with VL and 25 Post Kala-azar Dermal Leishmaniasis (PKDL) patients. Specificity was calculated on 250 healthy endemic controls, 250 healthy non endemic controls and 250 non leishmanial diseases like malaria. RESULTS:Our PCR assay had a sensitivity of 87.8% (95%CI: 84.1-89.8) using 200 µL of patient's peripheral-blood. Specificity was absolute in non-endemic healthy controls and in subjects with different diseases while in endemic controls it was 84% (95%CI: 78.9-88.0). Its overall specificity was 94.6% (95%CI-92.8-96.1). CONCLUSIONS:The PCR assay developed is sensitive enough to detect the 18S rRNA gene in an amount equivalent to a single parasite or less in a one million human cell environment. The high sensitivity of this PCR diagnostic test with relatively non-invasive peripheral blood sampling method opens up the possibility of its deployment in field for the routine diagnosis of VL. |
| 3. | PLoS One. 2011 May 3;6(5):e18724.Temperature-Induced Protein Secretion by Leishmania mexicana Modulates Macrophage Signalling and Function.Hassani K, Antoniak E, Jardim A, Olivier M.SourceDepartment of Microbiology and Immunology, McGill University, Montréal, Québec, Canada. AbstractProtozoan parasites of genus Leishmania are the causative agents of leishmaniasis. These digenetic microorganisms undergo a marked environmental temperature shift (TS) during transmission from the sandfly vector (ambient temperature, 25-26°C) to the mammalian host (37°C). We have observed that this TS induces a rapid and dramatic increase in protein release from Leishmania mexicana (cutaneous leishmaniasis) within 4 h. Proteomic identification of the TS-induced secreted proteins revealed 72 proteins, the majority of which lack a signal peptide and are thus thought to be secreted via nonconventional mechanisms. Interestingly, this protein release is accompanied by alterations in parasite morphology including an augmentation in the budding of exovesicles from its surface. Here we show that the exoproteome of L. mexicana upon TS induces cleavage and activation of the host protein tyrosine phosphatases, specifically SHP-1 and PTP1-B, in a murine bone-marrow-derived macrophage cell line. Furthermore, translocation of prominent inflammatory transcription factors, namely NF-κB and AP-1 is altered. The exoproteome also caused inhibition of nitric oxide production, a crucial leishmanicidal function of the macrophage. Overall, our results provide strong evidence that within early moments of interaction with the mammalian host, L. mexicana rapidly releases proteins and exovesicles that modulate signalling and function of the macrophage. These modulations can result in attenuation of the inflammatory response and deactivation of the macrophage aiding the parasite in the establishment of infection. |
| 4. | J Biol Chem. 2011 May 10. [Epub ahead of print]The LFR1 ferric iron reductase of Leishmania amazonensis is essential for the generation of infective parasite forms.Flannery AR , Huynh C, Mittra B, Mortara RA, Andrews NW.SourceUniversity of Maryland, United States; AbstractThe protozoan parasite Leishmania is the causative agent of serious human infections worldwide. The parasites alternate between insect and vertebrate hosts, and cause disease by invading macrophages, where they replicate. Parasites lacking the ferrous iron transporter LIT1 cannot grow intracellularly, indicating that a plasma membrane-associated mechanism for iron uptake is essential for the establishment of infections. Here we identify and functionally characterize a second member of the Leishmania iron acquisition pathway, the ferric iron reductase LFR1. The LFR1 gene is up-regulated under iron deprivation, and accounts for all the detectable ferric reductase activity exposed on the surface of L. amazonensis. LFR1-/- null mutants grow normally as promastigote insect stages, but are defective in differentiation into the vertebrate infective forms, metacyclic promastigotes and amastigotes. LFR1 over-expression partially restores the abnormal morphology of infective stages but markedly reduces parasite viability, precluding its ability to rescue LFR1-/- replication in macrophages. However, LFR1 over-expression is not toxic for amastigotes lacking the ferrous iron transporter LIT1, and rescues their axenic growth defect. This indicates that the Fe3+ reductase LFR1 functions upstream of LIT1, and suggests that LFR1 over-expression results in excessive Fe2+ production, which impairs parasite viability after intracellular transport by LIT1. |
| 5. | Infect Genet Evol. 2011 Apr 30. [Epub ahead of print]Natural Leishmania donovani/Leishmania aethiopica hybrids identified from Ethiopia.Odiwuor S, De Doncker S, Maes I, Dujardin JC, Van der Auwera G.SourceParasitology Department, Institute of Tropical Medicine Antwerp, Nationalestraat 155, Antwerp-2000, Belgium; Center for Clinical Research, Kenya Medical Research Institute, P.O. Box 20778, Nairobi-00202, Kenya; Department of Biomedical Sciences, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, Wilrijk-2610, Antwerp, Belgium. AbstractNatural hybridization events have been demonstrated between closely and distantly related Leishmania groups despite a predominantly clonal and endogamically sexual mode of reproduction. Here we report the first natural hybrid between Leishmania aethiopica and Leishmania donovani, as evidenced from the analysis of several clones from strain MHOM/ET/94/ABAUY. Targeted species-identification PCRs revealed the presence of both genotypes, and amplified fragment length polymorphisms indicated that the clones are genetically in an intermediate position between both parental species, being more closely related to L. aethiopica. The possible scenario facilitating hybrid formation is not clear, but is discussed in relation to epidemiological data. Copyright © 2011. Published by Elsevier B.V. |
| 6. | J Vector Ecol. 2011 Mar;36 Suppl 1:S138-43. doi: 10.1111/j.1948-7134.2011.00123.x.Sub-additive effect of conspecific eggs and frass on oviposition rate of Lutzomyia longipalpis and Phlebotomus papatasi.Wasserberg G, Rowton ED.SourceDivision of Entomology, Walter Reed Army Institute of Research, 530 Robert Grant Ave., Silver Spring, MD 20910, U.S.A. AbstractOviposition behavior is a fairly neglected aspect in our understanding of the biology of sand flies. In this study, we used a comparative approach using both new- and old-world species (Lutzomyia longipalpis and Phlebotomus papatasi) in choice and no-choice oviposition chambers to evaluate the effect of old sand fly colony remains (frass), conspecific eggs, and their combination on oviposition rates of these sand flies. We also tested the effect of egg washing with de-ionized water on oviposition rates. In both choice and no-choice experiments, sand fly species laid more eggs on a substrate containing frass. The effect of eggs alone was not significant but showed a positive trend. Furthermore, for both sand fly species, the effect of the combined treatment was sub-additive suggesting a potential inhibitory effect of one factor on the other. Egg washing did not have a significant effect. The choice and no-choice experimental designs did not differ in their outcomes suggesting the choice-design could serve as an effective high throughput method for screening oviposition attractants/stimulants. © 2011 The Society for Vector Ecology. |
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| 7. | J Evol Biol. 2011 Feb;24(2):354-62. doi: 10.1111/j.1420-9101.2010.02172.x. Epub 2010 Nov 19.Strain filtering and transmission of a mixed infection in a social insect.Ulrich Y, Sadd BM, Schmid-Hempel P.SourceETH Zürich, Institute of Integrative Biology, Zürich, Switzerland. yuko.ulrich@env.ethz.ch AbstractMixed-genotype infections have attracted considerable attention as drivers of pathogen evolution. However, experimental approaches often overlook essential features of natural host-parasite interactions, such as host heterogeneity, or the effects of between-host selection during transmission. Here, following inoculation of a mixed infection, we analyse the success of different strains of a trypanosome parasite throughout the colony cycle of its bumblebee host. We find that most colonies efficiently filter the circulating infection before it reaches the new queens, the only offspring that carry infections to the next season. A few colonies with a poor filtering ability thus contributed disproportionately to the parasite population in the next season. High strain diversity but not high infection intensity within colony was associated with an increased probability of transmission of the infection to new queens. Interestingly, the representation of the different strains changed dramatically over time, so that long-term parasite success could not be predicted from short-term observations. These findings highlight the shaping of within-colony parasite diversity through filtering as a crucial determinant of year-to-year pathogen transmission and emphasize the importance of host ecology and heterogeneity for disease dynamics. © 2010 The Authors. Journal of Evolutionary Biology © 2010 European Society For Evolutionary Biology. |
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