What's new for 'Trypanosomatids' in PubMed

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Sent on Saturday, 2012 May 26
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 15

1.	PLoS Negl Trop Dis. 2012 May;6(5):e1660. Epub 2012 May 22. Salivary Gland Transcriptomes and Proteomes of Phlebotomus tobbi and Phlebotomus sergenti, Vectors of Leishmaniasis. Rohoušová I, Subrahmanyam S, Volfová V, Mu J, Volf P, Valenzuela JG, Jochim RC. Source Department of Parasitology, Faculty of Science, Charles University in Prague, Prague, Czech Republic. Abstract BACKGROUND: Phlebotomus tobbi is a vector of Leishmania infantum, and P. sergenti is a vector of Leishmania tropica. Le. infantum and Le. tropica typically cause visceral or cutaneous leishmaniasis, respectively, but Le. infantum strains transmitted by P. tobbi can cause cutaneous disease. To better understand the components and possible implications of sand fly saliva in leishmaniasis, the transcriptomes of the salivary glands (SGs) of these two sand fly species were sequenced, characterized and compared. METHODOLOGY/PRINCIPAL FINDINGS: cDNA libraries of P. tobbi and P. sergenti female SGs were constructed, sequenced, and analyzed. Clones (1,152) were randomly picked from each library, producing 1,142 high-quality sequences from P. tobbi and 1,090 from P. sergenti. The most abundant, secreted putative proteins were categorized as antigen 5-related proteins, apyrases, hyaluronidases, D7-related and PpSP15-like proteins, ParSP25-like proteins, PpSP32-like proteins, yellow-related proteins, the 33-kDa salivary proteins, and the 41.9-kDa superfamily of proteins. Phylogenetic analyses and multiple sequence alignments of putative proteins were used to elucidate molecular evolution and describe conserved domains, active sites, and catalytic residues. Proteomic analyses of P. tobbi and P. sergenti SGs were used to confirm the identification of 35 full-length sequences (18 in P. tobbi and 17 in P. sergenti). To bridge transcriptomics with biology P. tobbi antigens, glycoproteins, and hyaluronidase activity was characterized. CONCLUSIONS: This analysis of P. sergenti is the first description of the subgenus Paraphlebotomus salivary components. The investigation of the subgenus Larroussius sand fly P. tobbi expands the repertoire of salivary proteins in vectors of Le. infantum. Although P. tobbi transmits a cutaneous form of leishmaniasis, its salivary proteins are most similar to other Larroussius subgenus species transmitting visceral leishmaniasis. These transcriptomic and proteomic analyses provide a better understanding of sand fly salivary proteins across species and subgenera that will be vital in vector-pathogen and vector-host research.
	PMID: 22629480 [PubMed - in process]
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2.	PLoS Negl Trop Dis. 2012 May;6(5):e1657. Epub 2012 May 22. Drug susceptibility in leishmania isolates following miltefosine treatment in cases of visceral leishmaniasis and post kala-azar dermal leishmaniasis. Bhandari V, Kulshrestha A, Deep DK, Stark O, Prajapati VK, Ramesh V, Sundar S, Schonian G, Dujardin JC, Salotra P. Source National Institute of Pathology, Indian Council of Medical Research, Safdarjung Hospital Campus, New Delhi, India. Abstract BACKGROUND: With widespread resistance to antimonials in Visceral Leishmaniasis (VL) in the Indian subcontinent, Miltefosine (MIL) has been introduced as the first line therapy. Surveillance of MIL susceptibility in natural populations of Leishmania donovani is vital to preserve it and support the VL elimination program. METHODOLOGY AND PRINCIPAL FINDINGS: We measured in vitro susceptibility towards MIL and paromomycin (PMM) in L. donovani isolated from VL and PKDL, pre- and post-treatment cases, using an amastigote-macrophage model. MIL susceptibility of post-treatment isolates from cured VL cases (n = 13, mean IC(50)±SD = 2.43±1.44 µM), was comparable (p>0.05) whereas that from relapses (n = 3, mean IC(50) = 4.72±1.99 µM) was significantly higher (p = 0.04) to that of the pre-treatment group (n = 6, mean IC(50) = 1.86±0.75 µM). In PKDL, post-treatment isolates (n = 3, mean IC(50) = 16.13±2.64 µM) exhibited significantly lower susceptibility (p = 0.03) than pre-treatment isolates (n = 5, mean IC(50) = 8.63±0.94 µM). Overall, PKDL isolates (n = 8, mean IC(50) = 11.45±4.19 µM) exhibited significantly higher tolerance (p<0.0001) to MIL than VL isolates (n = 22, mean IC(50) = 2.58±1.58 µM). Point mutations in the miltefosine transporter (LdMT) and its beta subunit (LdRos3) genes previously reported in parasites with experimentally induced MIL resistance were not present in the clinical isolates. Further, the mRNA expression profile of these genes was comparable in the pre- and post-treatment isolates. Parasite isolates from VL and PKDL cases were uniformly susceptible to PMM with respective mean IC(50) = 7.05±2.24 µM and 6.18±1.51 µM. CONCLUSION: The in vitro susceptibility of VL isolates remained unchanged at the end of MIL treatment; however, isolates from relapsed VL and PKDL cases had lower susceptibility than the pre-treatment isolates. PKDL isolates were more tolerant towards MIL in comparison with VL isolates. All parasite isolates were uniformly susceptible to PMM. Mutations in the LdMT and LdRos3 genes as well as changes in the expression of these genes previously correlated with experimental resistance to MIL could not be verified for the field isolates.
	PMID: 22629478 [PubMed - in process]
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3.	PLoS Negl Trop Dis. 2012 May;6(5):e1622. Epub 2012 May 22. Improved canine and human visceral leishmaniasis immunodiagnosis using combinations of synthetic peptides in enzyme-linked immunosorbent assay. Costa MM, Penido M, Dos Santos MS, Doro D, de Freitas E, Michalick MS, Grimaldi G, Gazzinelli RT, Fernandes AP. Source Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Instituto de Ciências Biológicas, Belo Horizonte, Minas Gerais, Brasil. Abstract BACKGROUND: Zoonotic visceral leishmaniasis (VL) is a severe infectious disease caused by protozoan parasites of the genus Leishmania and the domestic dogs are the main urban parasite reservoir hosts. In Brazil, indirect fluorescence antibody tests (IFAT) and indirect enzyme linked immunosorbent assay (ELISA) using promastigote extracts are widely used in epidemiological surveys. However, their sensitivity and specificity have often been compromised by the use of complex mixtures of antigens, which reduces their accuracy allowing the maintenance of infected animals that favors transmission to humans. In this context, the use of combinations of defined peptides appears favorable. Therefore, they were tested by combinations of five peptides derived from the previously described Leishmania diagnostic antigens A2, NH, LACK and K39. METHODOLOGY/PRINCIPAL FINDINGS: Combinations of peptides derived A2, NH, LACK and K39 antigens were used in ELISA with sera from 44 human patients and 106 dogs. Improved sensitivities and specificities, close to 100%, were obtained for both sera of patients and dogs. Moreover, high sensitivity and specificity were observed even for canine sera presenting low IFAT anti-Leishmania antibody titers or from asymptomatic animals. CONCLUSIONS/SIGNIFICANCE: The use of combinations of B cell predicted synthetic peptides derived from antigens A2, NH, LACK and K39 may provide an alternative for improved sensitivities and specificities for immunodiagnostic assays of VL.
	PMID: 22629475 [PubMed - in process]
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4.	PLoS Negl Trop Dis. 2012 May;6(5):e1533. Epub 2012 May 22. Disease Severity in Patients Infected with Leishmania mexicana Relates to IL-1β. Fernández-Figueroa EA, Rangel-Escareño C, Espinosa-Mateos V, Carrillo-Sánchez K, Salaiza-Suazo N, Carrada-Figueroa G, March-Mifsut S, Becker I. Source Departamento de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, México Distrito Federal, México. Abstract Leishmania mexicana can cause both localized (LCL) and diffuse (DCL) cutaneous leishmaniasis, yet little is known about factors regulating disease severity in these patients. We analyzed if the disease was associated with single nucleotide polymorphisms (SNPs) in IL-1β (-511), CXCL8 (-251) and/or the inhibitor IL-1RA (+2018) in 58 Mexican mestizo patients with LCL, 6 with DCL and 123 control cases. Additionally, we analyzed the in vitro production of IL-1β by monocytes, the expression of this cytokine in sera of these patients, as well as the tissue distribution of IL-1β and the number of parasites in lesions of LCL and DCL patients. Our results show a significant difference in the distribution of IL-1β (-511 C/T) genotypes between patients and controls (heterozygous OR), with respect to the reference group CC, which was estimated with a value of 3.23, 95% CI = (1.2, 8.7) and p-value = 0.0167), indicating that IL-1β (-511 C/T) represents a variable influencing the risk to develop the disease in patients infected with Leishmania mexicana. Additionally, an increased in vitro production of IL-1β by monocytes and an increased serum expression of the cytokine correlated with the severity of the disease, since it was significantly higher in DCL patients heavily infected with Leishmania mexicana. The distribution of IL-1β in lesions also varied according to the number of parasites harbored in the tissues: in heavily infected LCL patients and in all DCL patients, the cytokine was scattered diffusely throughout the lesion. In contrast, in LCL patients with lower numbers of parasites in the lesions, IL-1β was confined to the cells. These data suggest that IL-1β possibly is a key player determining the severity of the disease in DCL patients. The analysis of polymorphisms in CXCL8 and IL-1RA showed no differences between patients with different disease severities or between patients and controls.
	PMID: 22629474 [PubMed - in process]
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5.	PLoS One. 2012;7(5):e37639. Epub 2012 May 21. Additive and Transcript-Specific Effects of KPAP1 and TbRND Activities on 3' Non-Encoded Tail Characteristics and mRNA Stability in Trypanosoma brucei. Zimmer SL, McEvoy SM, Menon S, Read LK. Source Department of Microbiology and Immunology, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York, United States of America. Abstract Short, non-encoded oligo(A), oligo(U), or A/U tails can impact mRNA stability in kinetoplastid mitochondria. However, a comprehensive picture of the relative effects of these modifications in RNA stability is lacking. Furthermore, while the U-preferring exoribonuclease TbRND acts on U-tailed gRNAs, its role in decay of uridylated mRNAs has only been cursorily investigated. Here, we analyzed the roles of mRNA 3' tail composition and TbRND in RNA decay using cells harbouring single or double knockdown of TbRND and the KPAP1 poly(A) polymerase. Analysis of mRNA abundance and tail composition reveals dramatic and transcript-specific effects of adenylation and uridylation on mitochondrial RNAs. Oligo(A) and A-rich tails can stabilize a proportion of edited and never-edited RNAs. However, non-tailed RNAs are not inherently unstable, implicating additional stability determinants and/or spatial segregation of sub-populations of a given RNA in regulation of RNA decay. Oligo(U) tails, which have been shown to contribute to decay of some never-edited RNAs, are not universally destabilizing. We also show that RNAs display very different susceptibility to uridylation in the absence of KPAP1, a factor that may contribute to regulation of decay. Finally, 3' tail composition apparently impacts the ability of an RNA to be edited.
	PMID: 22629436 [PubMed - in process]
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6.	PLoS One. 2012;7(5):e37296. Epub 2012 May 22. A Quantitative 3D Motility Analysis of Trypanosoma brucei by Use of Digital In-line Holographic Microscopy. Weiße S, Heddergott N, Heydt M, Pflästerer D, Maier T, Haraszti T, Grunze M, Engstler M, Rosenhahn A. Source Applied Physical Chemistry, University of Heidelberg, Heidelberg, Germany. Abstract We present a quantitative 3D analysis of the motility of the blood parasite Trypanosoma brucei. Digital in-line holographic microscopy has been used to track single cells with high temporal and spatial accuracy to obtain quantitative data on their behavior. Comparing bloodstream form and insect form trypanosomes as well as mutant and wildtype cells under varying external conditions we were able to derive a general two-state-run-and-tumble-model for trypanosome motility. Differences in the motility of distinct strains indicate that adaption of the trypanosomes to their natural environments involves a change in their mode of swimming.
	PMID: 22629379 [PubMed - in process]
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7.	PLoS One. 2012;7(5):e36858. Epub 2012 May 18. Emergence and prevalence of human vector-borne diseases in sink vector populations. Rascalou G, Pontier D, Menu F, Gourbière S. Source UMR 5244 CNRS-UPVD Ecologie et Evolution des Interactions, Université de Perpignan Via Domitia, Perpignan, France. Abstract Vector-borne diseases represent a major public health concern in most tropical and subtropical areas, and an emerging threat for more developed countries. Our understanding of the ecology, evolution and control of these diseases relies predominantly on theory and data on pathogen transmission in large self-sustaining 'source' populations of vectors representative of highly endemic areas. However, there are numerous places where environmental conditions are less favourable to vector populations, but where immigration allows them to persist. We built an epidemiological model to investigate the dynamics of six major human vector borne-diseases in such non self-sustaining 'sink' vector populations. The model was parameterized through a review of the literature, and we performed extensive sensitivity analysis to look at the emergence and prevalence of the pathogen that could be encountered in these populations. Despite the low vector abundance in typical sink populations, all six human diseases were able to spread in 15-55% of cases after accidental introduction. The rate of spread was much more strongly influenced by vector longevity, immigration and feeding rates, than by transmission and virulence of the pathogen. Prevalence in humans remained lower than 5% for dengue, leishmaniasis and Japanese encephalitis, but substantially higher for diseases with longer duration of infection; malaria and the American and African trypanosomiasis. Vector-related parameters were again the key factors, although their influence was lower than on pathogen emergence. Our results emphasize the need for ecology and evolution to be thought in the context of metapopulations made of a mosaic of sink and source habitats, and to design vector control program not only targeting areas of high vector density, but working at a larger spatial scale.
	PMID: 22629337 [PubMed - in process]
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8.	PLoS One. 2012;7(5):e35748. Epub 2012 May 22. Naturally Occurring Culturable Aerobic Gut Flora of Adult Phlebotomus papatasi, Vector of Leishmania major in the Old World. Mukhopadhyay J, Braig HR, Rowton ED, Ghosh K. Source Division of Entomology, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America. Abstract BACKGROUND: Cutaneous leishmaniasis is a neglected, vector-borne parasitic disease and is responsible for persistent, often disfiguring lesions and other associated complications. Leishmania, causing zoonotic cutaneous leishmaniasis (ZCL) in the Old World are mainly transmitted by the predominant sand fly vector, Phlebotomus papatasi. To date, there is no efficient control measure or vaccine available for this widespread insect-borne infectious disease. METHODOLOGY/PRINCIPAL FINDINGS: A survey was carried out to study the abundance of different natural gut flora in P. papatasi, with the long-term goal of generating a paratransgenic sand fly that can potentially block the development of Leishmania in the sand fly gut, thereby preventing transmission of leishmania in endemic disease foci. Sand flies, in particular, P. papatasi were captured from different habitats of various parts of the world. Gut microbes were cultured and identified using 16S ribosomal DNA analysis and a phylogenetic tree was constructed. We found variation in the species and abundance of gut flora in flies collected from different habitats. However, a few Gram-positive, nonpathogenic bacteria including Bacillus flexus and B. pumilus were common in most of the sites examined. CONCLUSION/SIGNIFICANCE: Our results indicate that there is a wide range of variation of aerobic gut flora inhabiting sand fly guts, which possibly reflect the ecological condition of the habitat where the fly breeds. Also, some species of bacteria (B. pumilus, and B. flexus) were found from most of the habitats. Important from an applied perspective of dissemination, our results support a link between oviposition induction and adult gut flora.
	PMID: 22629302 [PubMed - in process]
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9.	Biol Chem. 2012 May 1;393(6):513-24. doi: 10.1515/hsz-2011-0255. Mitochondrial protein import pathways are functionally conserved among eukaryotes despite compositional diversity of the import machineries. Eckers E, Cyrklaff M, Simpson L, Deponte M. Abstract Abstract Mitochondrial protein import (MPI) is essential for the biogenesis of mitochondria in all eukaryotes. Current models of MPI are predominantly based on experiments with one group of eukaryotes, the opisthokonts. Although fascinating genome database-driven hypotheses on the evolution of the MPI machineries have been published, previous experimental research on non-opisthokonts usually focused on the analysis of single pathways or components in, for example, plants and parasites. In this study, we have established the kinetoplastid parasite Leishmania tarentolae as a model organism for the comprehensive analysis of non-opisthokont MPI into all four mitochondrial compartments. We found that opisthokont marker proteins are efficiently imported into isolated L. tarentolae mitochondria. Vice versa, L. tarentolae marker proteins of all compartments are also imported into mitochondria from yeast. The results are remarkable because only a few of the more than 25 classical components of the opisthokont MPI machineries are found in parasite genome databases. Our results demonstrate that different MPI pathways are functionally conserved among eukaryotes despite significant compositional differences of the MPI machineries. Moreover, our model system could lead to the identification of significantly altered or even novel MPI components in non-opisthokonts. Such differences might serve as starting points for drug development against parasitic protists.
	PMID: 22628314 [PubMed - in process]
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10.	Exp Parasitol. 2012 May 21. [Epub ahead of print] Enhancement in therapeutic efficacy of miltefosine in combination with synthetic Bacterial lipopeptide, Pam3Cys against experimental Visceral Leishmaniasis. Shakya N, Sane SA, Vishwakarma P, Gupta S. Source Division of Parasitology, Central Drug Research Institute (CSIR), Lucknow, India. Abstract Existing drugs for Visceral Leishmaniasis (VL) are partially effective, toxic, having high cost and long term treatment. Their efficacies are also compromised due to suppression of immune function associated during the course of infection. Combination therapy including a potential and safe immunostimulant with lower doses of effective drug has proven as a significant approach which is more effective than immunotherapy or drug therapy alone. In the present study, we have used the combination of Pam3Cys (an in-built immunoadjuvant and TLR2 ligand) and miltefosine. Initially dose optimization of both the agents was carried out and after that, antileishmanial effect of their combination was evaluated. All experiments were done in BALB/c mouse model. The immunomodulatory role of Pam3Cys on the immune functions of the host receiving combination treatment was also determined using immunological and biochemical parameters viz. phagocytosis, Th1/Th2 cytokines and production of ROS, RNS and H(2)O(2). Combination group showed significant enhancement in parasitic inhibition as compared to groups receiving miltefosine and Pam3Cys separately. Enhanced production of Th1 cytokines as well as ROS, RNS and H(2)O(2) was witnessed during the study of immunological alterations. Remarkable increase in phagocytosis index was also observed. Thus, the risk of development of drug resistance against miltefosine can be resolved through using low doses of it and Pam3Cys (single-dose) in combination and also provide a promising alternative for cure of leishmaniasis, with a pronounced transformation of the host immune response. Copyright © 2012. Published by Elsevier Inc.
	PMID: 22626518 [PubMed - as supplied by publisher]
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