Tuesday, January 24, 2012

What's new for 'Trypanosomatids' in PubMed

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Sent on Tuesday, 2012 January 24
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 10

1. J Biol Chem. 2012 Jan 20. [Epub ahead of print]

A Mitochondrial membrane complex that contains proteins necessary for tRNA import in Trypanosoma brucei.

Seidman D, Johsnon D, Gerbasi V, Golden D, Orlando R, Hajduk S.

Source

The University of Georgia, United States;

Abstract

The mitochondrial genome of Trypanosoma brucei does not contain genes encoding tRNAs, instead this protozoan parasite must import nuclear encoded tRNAs from the cytosol for mitochondrial translation. Previously, it has been shown that mitochondrial tRNA import requires ATP hydrolysis and a proteinaceous mitochondrial membrane component. However, little is known about the mitochondrial membrane proteins involved in tRNA binding and translocation into the mitochondrion. Here we report the purification of a mitochondrial membrane complex using tRNA affinity purification and have identified several protein components of the putative tRNA translocon by mass spectrometry. Using an in vivo tRNA import assay, in combination with RNA interference, we have verified that two of these proteins, Tb11.01.4590 and Tb09.v1.0420, are involved in mitochondrial tRNA import. Using PTP-tagged Tb11.01.4590, additional associated proteins were identified including Tim17 and other mitochondrial proteins necessary for mitochondrial protein import. Results presented here identify and validate two novel protein components of the putative tRNA translocon and provide additional evidence that mitochondrial tRNA and protein import have shared components in trypanosomes.

PMID:
22267727
[PubMed - as supplied by publisher]
2. Bioorg Med Chem. 2011 Dec 27. [Epub ahead of print]

Quinol derivatives as potential trypanocidal agents.

Capes A, Patterson S, Wyllie S, Hallyburton I, Collie IT, McCarroll AJ, Stevens MF, Frearson JA, Wyatt PG, Fairlamb AH, Gilbert IH.

Source

Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.

Abstract

Quinols have been developed as a class of potential anti-cancer compounds. They are thought to act as double Michael acceptors, forming two covalent bonds to their target protein(s). Quinols have also been shown to have activity against the parasite Trypanosoma brucei, the causative organism of human African trypanosomiasis, but they demonstrated little selectivity over mammalian MRC5 cells in a counter-screen. In this paper, we report screening of further examples of quinols against T. brucei. We were able to derive an SAR, but the compounds demonstrated little selectivity over MRC5 cells. In an approach to increase selectivity, we attached melamine and benzamidine motifs to the quinols, because these moieties are known to be selectively concentrated in the parasite by transporter proteins. In general these transporter motif-containing analogues showed increased selectivity; however they also showed reduced levels of potency against T. brucei.

Copyright © 2011 Elsevier Ltd. All rights reserved.

PMID:
22264753
[PubMed - as supplied by publisher]
3. Lipids Health Dis. 2012 Jan 20;11(1):13. [Epub ahead of print]

Synthesis of lipophilic tyrosyl esters derivatives and assessment of their antimicrobial and antileishmania activities.

Aissa I, Sghair RM, Bouaziz M, Laouini D, Sayadi S, Gargouri Y.

Abstract

ABSTRACT:

BACKGROUND:

Preparation of tyrosyl lipophilic derivatives was carried out as a response to the food, cosmetic and pharmaceutical industries' increasing demand for new lipophilic antioxidants.

RESULTS:

A large series of tyrosyl esters (TyC2 to TyC18:1) with increasing lipophilicity was synthesized in a good yield using lipase from Candida antarctica (Novozyme 435). Spectroscopic analyses of purified esters showed that the tyrosol was esterified on the primary hydroxyl group. Synthetized compounds were evaluated for either their antimicrobial activity, by both diffusion well and minimal inhibition concentration (MIC) methods, or their antileishmanial activity against Leishmania major and Leishmania infantum parasite species. Among all the tested compounds, our results showed that only TyC8, TyC10 and TyC12 exhibited antibacterial and antileishmanial activities. When MIC and IC50 values were plotted against the acyl chain length of each tyrosyl derivative, TyC10 showed a parabolic shape with a minimum value. This nonlinear dependency with the increase of the chain length indicates that biological activities are probably associated to the surfactant effectiveness of lipophilic derivatives.

CONCLUSION:

These results open up potential applications to use medium tyrosyl derivatives surfactants, antioxidants, antimicrobial and antileishmanial compounds in cosmetic, food and pharmaceutical industries.

PMID:
22264330
[PubMed - as supplied by publisher]
4. Vet Rec. 2011 Nov 19;169(21):541.

New approach to cattle vaccination.

[No authors listed]
PMID:
22102345
[PubMed - indexed for MEDLINE]
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5. Proc Natl Acad Sci U S A. 2011 Nov 29;108(48):19288-92. Epub 2011 Nov 14.

Socially tra nsmitted gut microbiota protect bumble bees against an intestinal parasite.

Koch H, Schmid-Hempel P.

Source

Institute of Integrative Biology, Swiss Federal Institute of Technology, ETH, Zürich, CH-8092 Zürich, Switzerland.

Abstract

Populations of important pollinators, such as bumble bees and honey bees, are declining at alarming rates worldwide. Parasites are likely contributing to this phenomenon. A distinct resident community of bacteria has recently been identified in bumble bees and honey bees that is not shared with related solitary bee species. We now show that the presence of these microbiota protects bee hosts against a widespread and highly virulent natural parasite (Crithidia bombi) in an experimental setting. We add further support to this antagonistic relationship from patterns found in field data. For the successful establishment of these microbiota and a protective effect, exposure to feces from nest mates was needed after pupal eclosion. Transmission of beneficial gut bacteria could therefore represent an important benefit of sociality. Our results stress the importance of considering the host microbiota as an "extended immune phenotype" in addition to the host immune system itself and provide a unique perspective to understanding bees in health and disease.

PMCID: PMC3228419
[Available on 2012/5/29]
PMID:
22084077
[PubMed - indexed for MEDLINE]
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6. Am J Pathol. 2011 Oct;179(4):1894-904. Epub 2011 Aug 3.

Mast cell function and death in Trypanosoma cruzi infection.

Meuser-Batista M, Corrêa JR, Carvalho VF, de Carvalho Britto CF, da Cruz Moreira O, Batista MM, Soares MJ, Filho FA, E Silva PM, Lannes-Vieira J, Silva RC, Henriques-Pons A.

Source

Laboratório de Inovações em Terapias, Ensino, e Bioprodutos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. meuser@ioc.fiocruz.br

Abstract

Although the roles of mast cells (MCs) are essential in many inflammatory and fibrotic diseases, their role in Trypanosoma cruzi-induced cardiomyopathy is unexplored. In this study, we treated infected CBA mice with cromolyn, an MC stabilizer, and observed much greater parasitemia and interferon-γ levels, higher mortality, myocarditis, and cardiac damage. Although these data show that MCs are important in controlling acute infection, we observed MC apoptosis in the cardiac tissue and peritoneal cavity of untreated mice. In the heart, pericardial mucosal MC die, perhaps because of reduced amounts of local stem cell factor. Using RT-PCR in purified cardiac MCs, we observed that infection induced transcription of P2X(7) receptor and Fas, two molecules reportedly involved in cell death and inflammatory regulation. In gld/gld mice (FasL(-/-)), apoptosis of cardiac, but not peritoneal, MCs was decreased. Conversely, infection of P2X(7)(-/-) mice led to reduced peritoneal, but not cardiac, MC death. These data illustrate the immunomodulatory role played by MCs in T. cruzi infection and the complexity of molecular interactions that control inflammatory pathways in different tissues and compartments.

Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

PMCID: PMC3181382
[Available on 2012/10/1]
PMID:
21819958
[PubMed - indexed for MEDLINE]
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7. Asian Pac J Trop Med. 2011 Mar;4(3):234-40. Epub 2011 Apr 12.

Choice of providers for treating a neglected tropical disease: an empirical anal ysis of kala azar in Nepal.

Adhikari SR, Supakankunti S, Khan MM.

Source

Patan Multiple Campus, Tribhuvan University, Nepal. sssadhikari@yahoo.com

Abstract

OBJECTIVE:

To examine the choice of healthcare providers for treating kala azar (KA) in Nepal.

METHODS:

Information was collected from clinically diagnosed KA patients seeking care from public hospitals located in KA endemic districts. The survey collected information from more than 25 percent of total KA cases in the country. For empirical estimation of probability of choosing a provider-type as a first contact healthcare provider, a multinomial logit model was defined with five alternative options with self care as the reference category.

RESULTS:

The empirical model found that price of medical care services, income of households, knowledge of patients on KA and KA treatment, borrowing money, age of patient, perceived quality of provider types, etc. determine the likelihood of seeking care from the alternative options considered in the analysis. All variables have expected signs and are consistent with earlier studies. The price and income elasticity were found to be very high indicating that poorer households are very sensitive to price and income changes, even for a severe disease like KA. Using the empirical models, we have analyzed two policy instruments: demand side financing and interventions to improve the knowledge index about KA.

CONCLUSIONS:

Due to high price elasticity of KA care and high spillover effects of KA on the society, policy makers may consider demand side financing as an instrument to encourage utilization of public hospitals.

Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

PMID:
21771461
[PubMed - indexed for MEDLINE]
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8. Microbiology. 2011 Oct;157(Pt 10):2818-30. Epub 2011 Jul 14.

Characterization of a porin channel in the endosymbiont of the trypanosomatid p rotozoan Crithidia deanei.

Andrade Ida S, Vianez-Júnior JL, Goulart CL, Homblé F, Ruysschaert JM, Almeida von Krüger WM, Bisch PM, de Souza W, Mohana-Borges R, Motta MC.

Source

Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

Abstract

Crithidia deanei is a trypanosomatid protozoan that harbours a symbiotic bacterium. The partners maintain a mutualistic relationship, thus constituting an excellent model for studying metabolic exchanges between the host and the symbiont, the origin of organelles and cellular evolution. According to molecular analysis, symbionts of different trypanosomatid species share high identity and descend from a common ancestor, a β-proteobacterium of the genus Bordetella. The endosymbiont is surrounded by two membranes, like Gram-negative bacteria, but its envelope presents special features, since phosphatidylcholine is a major membrane component and the peptidoglycan layer is highly reduced, as described in other obligate intracellular bacteria. Like the process that generated mitochondria and plastids, the endosymbiosis in trypanosomatids depends on pathways that facilitate the intensive metabolic exchanges between the bacterium and the host protozoan. A search of the annotated symbiont genome database identified one sequence with identity to porin-encoding genes of the genus Bordetella. Considering that the symbiont outer membrane has a great accessibility to cytoplasm host factors, it was important to characterize this single porin-like protein using biochemical, molecular, computational and ultrastructural approaches. Antiserum against the recombinant porin-like molecule revealed that it is mainly located in the symbiont envelope. Secondary structure analysis and comparative modelling predicted the protein 3D structure as an 18-domain β-barrel, which is consistent with porin channels. Electrophysiological measurements showed that the porin displays a slight preference for cations over anions. Taken together, the data presented herein suggest that the C. deanei endosymbiont porin is phylogenetically and structurally similar to those described in Gram-negative bacteria, representing a diffusion channel that might contribute to the exchange of nutrients and metabolic precursors between the symbiont and its host cell.

PMID:
21757490
[PubMed - indexed for MEDLINE]
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9. Int J Parasitol. 2008 Nov;38(13):1533-43. Epub 2008 May 24.

Molecular epidemiology of domestic and sylvatic Trypanoso ma cruzi infection in rural northwestern Argentina.

Cardinal MV, Lauricella MA, Ceballos LA, Lanati L, Marcet PL, Levin MJ, Kitron U, Gürtler RE, Schijman AG.

Source

Laboratorio de Eco-Epidemiología, Departamento de Ecología, Genética y Evolución, Universidad de Buenos Aires, Buenos Aires, Argentina.

Abstract

Genetic diversity of Trypanosoma cruzi populations and parasite transmission dynamics have been well documented throughout the Americas, but few studies have been conducted in the Gran Chaco ecoregion, one of the most highly endemic areas for Chagas disease, caused by T. cruzi. In this study, we assessed the distribution of T. cruzi lineages (identified by PCR strategies) in Triatoma infestans, domestic dogs, cats, humans and sylvatic mammals from two neighbouring rural areas with different histories of transmission and vector control in northern Argentina. Lineage II predominated amongst the 99 isolates characterised and lineage I amongst the six isolates obtained from sylvatic mammals. T. cruzi lineage IIe predominated in domestic habitats; it was found in 87% of 54 isolates from Tr. infestans, in 82% of 33 isolates from dogs, and in the four cats found infected. Domestic and sylvatic cycles overlapped in the study area in the late 1980s, when intense domestic transmission occurred, and still overlap marginally. The introduction of T. cruzi from sylvatic into domestic habitats is likely to occur very rarely in the current epidemiological context. The household distribution of T. cruzi lineages showed that Tr. infestans, dogs and cats from a given house compound shared the same parasite lineage in most cases. Based on molecular evidence, this result lends further support to the importance of dogs and cats as domestic reservoir hosts of T. cruzi. We believe that in Argentina, this is the first time that lineage IIc has been isolated from naturally infected domestic dogs and Tr. infestans.

PMCID: PMC3143243
Free PMC Article
PMID:
18585717
[PubMed - indexed for MEDLINE]
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10. Int J Parasitol. 2008 Nov;38(13):1481-92. Epub 2008 May 21.

Some components of the cardiac β-adrenergic system are altered in the chronic indeterminate form of experimental Trypanosoma cruzi infection.

Silvina Lo Presti M, Walter Rivarola H, Bustamante JM, Fernández AR, Enders JE, Levin G, Juaneda E, Fretes R, Fernanda Triquell M, Paglini-Oliva PA.

Source

Cátedra de Física Biomédica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Santa Rosa 1085, PC 5000 Córdoba, Argentina.

Abstract

The chronic indeterminate form of Trypanosoma cruzi infection could be the key to knowing which patients will develop chagasic myocardiopathy. Infected mice present a period in which cardiac functional and structural alterations are different from those described for acute or chronic phases. We studied some components of the cardiac β-adrenergic system in mouse hearts infected with T. cruzi Tulahuen strain or SGO-Z12 isolate during the chronic indeterminate phase of infection. We determined: (i) the primary messenger (epinephrine and norepinephrine) levels in plasma by reverse-phase-HPLC; (ii) the cardiac β-adrenergic receptors' (β-AR) density and affinity by binding with tritiated dihidroalprenolol and by immunofluorescence; (iii) the cardiac concentration of the second messenger (cAMP) (by ELISA) given its importance for the phosphorylation of the proteins involved in cardiac contraction; (iv) the cardiac contractility and functional studies of the β-ARs as a response to the ligand binding to the receptor; and (v) the left ventricular ejection fraction as a measure of in vivo cardiac function. Plasma catecholamines levels remained similar to those found in uninfected controls. The β-ARs' affinity decreased in both infected groups compared with the uninfected group (P<0.05) while the receptors' density increased only in the SGO-Z12 group (P<0.01). Cyclic AMP levels were higher in both infected groups (P<0.01) relative to controls, and were higher in SGO-Z12-infected mice compared with those infected with the Tulahuen strain. However, the basal contractile force remained unchanged and the response to catecholamines only increased in the Tulahuen group (P<0.05). The left ventricular ejection fraction, on the other hand, was diminished in SGO-Z12-infected mice. Heterogeneity between T. cruzi strains determine, in the chronic indeterminate form, alterations in the signaling pathways of the β-adrenergic system at different levels: (i) between catecholamines and the β(1)-receptors; (ii) between the receptors' activation and the adenylyl-cyclase activation; and/or (iii) between cAMP and the contractile response.

PMID:
18582889
[PubMed - indexed for MEDLINE]
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