What's new for 'Trypanosomatids' in PubMed

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Sent on Thursday, 2012 February 23
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 12

1.	Sci Rep. 2012;2:254. Epub 2012 Feb 9. Ethanolamine phosphoglycerol attachment to eEF1A is not essential for normal growth of Trypanosoma brucei. Greganova E, Bütikofer P. Abstract Eukaryotic elongation factor 1A (eEF1A) is the only protein modified by ethanolamine phosphoglycerol (EPG). In mammals and plants, EPG is attached to conserved glutamate residues located in eEF1A domains II and III, whereas in the unicellular eukaryote, Trypanosoma brucei, a single EPG moiety is attached to domain III. A biosynthetic precursor of EPG and structural requirements for EPG attachment to T. brucei eEF1A have been reported, but the role of this unique protein modification in cellular growth and eEF1A function has remained elusive. Here we report, for the first time in a eukaryotic cell, a model system to study potential roles of EPG. By down-regulation of EF1A expression and subsequent complementation of eEF1A function using conditionally expressed exogenous eEF1A (mutant) proteins, we show that eEF1A lacking EPG complements trypanosomes deficient in endogenous eEF1A, demonstrating that EPG attachment is not essential for normal growth of T. brucei in culture.
	PMID: 22355766 [PubMed - in process]

2.	PLoS One. 2012;7(2):e31344. Epub 2012 Feb 15. A MAP6-Related Protein Is Present in Protozoa and Is Involved in Flagellum Motility. Dacheux D, Landrein N, Thonnus M, Gilbert G, Sahin A, Wodrich H, Robinson DR, Bonhivers M. Source Microbiologie Fondamentale et Pathogénicité, Université de Bordeaux, UMR 5234, Bordeaux, France. Abstract In vertebrates the microtubule-associated proteins MAP6 and MAP6d1 stabilize cold-resistant microtubules. Cilia and flagella have cold-stable microtubules but MAP6 proteins have not been identified in these organelles. Here, we describe TbSAXO as the first MAP6-related protein to be identified in a protozoan, Trypanosoma brucei. Using a heterologous expression system, we show that TbSAXO is a microtubule stabilizing protein. Furthermore we identify the domains of the protein responsible for microtubule binding and stabilizing and show that they share homologies with the microtubule-stabilizing Mn domains of the MAP6 proteins. We demonstrate, in the flagellated parasite, that TbSAXO is an axonemal protein that plays a role in flagellum motility. Lastly we provide evidence that TbSAXO belongs to a group of MAP6-related proteins (SAXO proteins) present only in ciliated or flagellated organisms ranging from protozoa to mammals. We discuss the potential roles of the SAXO proteins in cilia and flagella function.
	PMID: 22355359 [PubMed - in process]

3.	Korean J Parasitol. 2011 Dec;49(4):357-64. Epub 2011 Dec 16. Use of In Vivo and In Vitro Systems to Select Leishmania amazonensis Expressing Green Fluorescent Protein. Costa Sdos S, de Assis Golim M, Rossi-Bergmann B, Costa FT, Giorgio S. Source Department of Animal Biology, Biology Institute, Universidade Estadual de Campinas Caixa Postal 6109, Cep 13.083-970, Campinas, São Paulo, Brazil. Abstract Various Leishmania species were engineered with green fluorescent protein (GFP) using episomal vectors that encoded an antibiotic resistance gene, such as aminoglycoside geneticin sulphate (G418). Most reports of GFP-Leishmania have used the flagellated extracellular promastigote, the stage of parasite detected in the midgut of the sandfly vector; fewer studies have been performed with amastigotes, the stage of parasite detected in mammals. In this study, comparisons were made regarding the efficiency for in vitro G418 selection of GFP-Leishmania amazonensis promastigotes and amastigotes and the use of in vivo G418 selection. The GFP-promastigotes retained episomal plasmid for a prolonged period and G418 treatment was necessary and efficient for in vitro selection. In contrast, GFP-amastigotes showed low retention of the episomal plasmid in the absence of G418 selection and low sensitivity to antibiotics in vitro. The use of protocols for G418 selection using infected BALB/c mice also indicated low sensitivity to antibiotics against amastigotes in cutaneous lesions.
	PMID: 22355202 [PubMed - in process]

4.	Proc Natl Acad Sci U S A. 2012 Feb 21. [Epub ahead of print] Aerobic kinetoplastid flagellate Phytomonas does not require heme for viability. Koreny L, Sobotka R, Kovárová J, Gnipová A, Flegontov P, Horváth A, Oborník M, Ayala FJ, Lukes J. Source Biology Centre, Institute of Parasitology, Czech Academy of Sciences and Faculty of Science, University of South Bohemia, 370 05 České Budějovice, Czech Republic. Abstract Heme is an iron-coordinated porphyrin that is universally essential as a protein cofactor for fundamental cellular processes, such as electron transport in the respiratory chain, oxidative stress response, or redox reactions in various metabolic pathways. Parasitic kinetoplastid flagellates represent a rare example of organisms that depend on oxidative metabolism but are heme auxotrophs. Here, we show that heme is fully dispensable for the survival of Phytomonas serpens, a plant parasite. Seeking to understand the metabolism of this heme-free eukaryote, we searched for heme-containing proteins in its de novo sequenced genome and examined several cellular processes for which heme has so far been considered indispensable. We found that P. serpens lacks most of the known hemoproteins and does not require heme for electron transport in the respiratory chain, protection against oxidative stress, or desaturation of fatty acids. Although heme is still required for the synthesis of ergosterol, its precursor, lanosterol, is instead incorporated into the membranes of P. serpens grown in the absence of heme. In conclusion, P. serpens is a flagellate with unique metabolic adaptations that allow it to bypass all requirements for heme.
	PMID: 22355128 [PubMed - as supplied by publisher]

5.	Mol Biochem Parasitol. 2012 Feb 14. [Epub ahead of print] Trypanosomal histone γH2A and the DNA damage response. Glover L, Horn D. Source London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK. Abstract DNA damage and repair in trypanosomatids impacts virulence, drug resistance and antigenic variation but, currently, little is known about DNA damage responses or cell cycle checkpoints in these divergent protozoa. One of the earliest markers of DNA damage in eukaryotes is γH2A(X), a serine phosphorylated histone H2A (variant). Here, we report the identification and initial characterization of γH2A in Trypanosoma brucei. We identified Thr(130) within the replication-dependent histone H2A as a candidate phosphorylation site and found that the abundance of this trypanosomal γH2A increased in vivo in response to DNA damage. Nuclear γH2A foci mark the sites of putative natural replication fork stalling, sites of meganuclease-induced DNA double strand breaks and sites of methyl methanesulphonate-induced DNA damage. Naturally occurring and meganuclease-induced γH2A and RAD51 double-positive repair foci are typically found in S-phase or G(2) nuclei. The results link trypanosomal γH2A, with an unusual histone modification motif, to DNA damage sensing and mitotic checkpoint signaling. Copyright © 2012. Published by Elsevier B.V.
	PMID: 22353557 [PubMed - as supplied by publisher]

6.	Curr Top Med Chem. 2012 Feb 14. [Epub ahead of print] A Review of QSAR studies to Discover New Drug-like Compounds Actives against Leishmaniasis and Trypanosomiasis. Castillo-Garit JA, Abad C, Rodríguez-Borges JE, Marrero-Ponce Y, Torrens F. Source Applied Chemistry Research Center, Faculty of Chemistry-Pharmacy and Department of Drug Design, Chemical Bioactive Center, Central University of Las Villas, Santa Clara, 54830, Villa Clara, Cuba. jacgarit@yahoo.es, juancg.22@gmail.com or juancg@uclv.edu.cu. Abstract The neglected tropical diseases (NTDs) affect more than one billion people (one-sixth of the world's population) and occur primarily in undeveloped countries in sub-Saharan Africa, Asia, and Latin America. Available drugs for these diseases are decades old and present an important number of limitations, especially high toxicity and, more recently, the emergence of drug resistance. In the last decade several Quantitative Structure-Activity Relationship (QSAR) studies have been developed in order to identify new organic compounds with activity against the parasites responsible for these diseases, which are reviewed in this paper. The topics summarized in this work are: 1) QSAR studies to identify new organic compounds actives against Chaga's disease; 2) Development of QSAR studies to discover new antileishmanial drusg; 3) Computational studies to identify new drug-like compounds against human African trypanosomiasis. Each topic include the general characteristics, epidemiology and chemotherapy of the disease as well as the main QSAR approaches to discovery/identification of new actives compounds for the corresponding neglected disease. The last section is devoted to a new approach know as multi-target QSAR models developed for antiparasitic drugs specifically those actives against trypanosomatid parasites. At present, as a result of these QSAR studies several promising compounds, active against these parasites, are been indentify. However, more efforts will be required in the future to develop more selective (specific) useful drugs.
	PMID: 22352913 [PubMed - as supplied by publisher]

7.	J Med Chem. 2012 Feb 21. [Epub ahead of print] Synthesis, Biological Evaluation and Structure-Activity Relationships of N-Benzoyl-2-hydroxybenzamides as Agents Active against P. falciparum (K1 strain), Trypanosomes, and Leishmania. Stec J, Huang Q, Pieroni M, Kaiser M, Fomovska A, Mui E, Witola WH, Bettis S, McLeod R, Brun R, Kozikowski AP. Abstract In our efforts to identify novel chemical scaffolds for the development of new anti-protozoal drugs, a compound library was screened against T. gondii tachyzoites with activity discovered for N-(4-ethylbenzoyl)-2-hydroxybenzamide 1a against T. gondii as described elsewhere.1 Synthesis of a compound set was guided by T. gondii SAR with 1r found to be superior for T. gondii, also active against Thai and Sierra Leone strains of P. falciparum, and with superior ADMET properties as described elsewhere.1 Herein, synthesis methods and details of the chemical analysis of the compounds in this series are described. Further, this series of N-benzoyl-2-hydroxybenzamides was re-purposed for testing against four other protozoan parasites: T. b. rhodesiense, T. cruzi, L. donovani, and P. falciparum (K1 isolate). Structure-activity analyses led to the identification of compounds in this set with excellent anti-leishmanial activity (compound 1d). Overall, compound 1r was the best and had activity 21-fold superior to that of the standard anti-malarial drug chloroquine against the K1 P. falciparum isolate.
	PMID: 22352841 [PubMed - as supplied by publisher]

8.	Z Naturforsch C. 2011 Nov-Dec;66(11-12):541-6. Trypanocidal and cytotoxic effects of 30 Ethiopian medicinal plants. Nibret E, Wink M. Source Institut für Pharmazie und Molekulare Biotechnologie, Universität Heidelberg, Im Neuenheimer Feld 364, D-69120, Heidelberg, Germany. Abstract Trypanocidal and cytotoxic effects of traditionally used medicinal plants of Ethiopia were evaluated. A total of 60 crude plant extracts were prepared from 30 plant species using CH2Cl2 and MeOH. Effect upon cell proliferation by the extracts, for both bloodstream forms of Trypanosoma brucei brucei and human leukaemia HL-60 cells, was assessed using resazurin as vital stain. Of all CH2Cl2 and MeOH extracts evaluated against the trypanosomes, the CH2Cl2 extracts from five plants showed trypanocidal activity with an IC50 value below 20 microg/mL: Dovyalis abyssinica (Flacourtiaceae), IC50 = 1.4 microg/mL; Albizia schimperiana (Fabaceae), IC50 = 7.2 microg/mL; Ocimum urticifolium (Lamiaceae), IC50 = 14.0 microg/mL; Acokanthera schimperi (Apocynaceae), IC50 = 16.6 microg/mL; and Chenopodium ambrosioides (Chenopodiaceae), IC50 = 17.1 microg/mL. A pronounced and selective killing of trypanosomes with minimal toxic effect on human cells was exhibited by Dovyalis abyssinica (CH2Cl2 extract, SI = 125.0; MeOH extract, SI = 57.7) followed by Albizia schimperiana (CH2Cl2 extract, SI = 31.3) and Ocimum urticifolium (MeOH extract, SI = 16.0). In conclusion, the screening of 30 Ethiopian medicinal plants identified three species with good antitrypanosomal activities and low toxicity towards human cells. Dovyalis abyssinica might be a promising candidate for phytotherapy of trypanosomiasis.
	PMID: 22351978 [PubMed - in process]

9.	PLoS Negl Trop Dis. 2011 Nov;5(11):e1375. Epub 2011 Nov 1. Crystal structure of the complex mAb 17.2 and the C-terminal region of Trypanosoma cruzi P2β protein: implications in cross-reactivity. Pizarro JC, Boulot G, Bentley GA, Gómez KA, Hoebeke J, Hontebeyrie M, Levin MJ, Smulski CR. Source Unité d'Immunologie Structurale, Institut Pasteur, Paris, France. Abstract Patients with Chronic Chagas' Heart Disease possess high levels of antibodies against the carboxyl-terminal end of the ribosomal P2ß protein of Trypanosoma cruzi (TcP2ß). These antibodies, as well as the murine monoclonal antibody (mAb) 17.2, recognize the last 13 amino acids of TcP2ß (called the R13 epitope: EEEDDDMGFGLFD) and are able to cross-react with, and stimulate, the ß1 adrenergic receptor (ß1-AR). Indeed, the mAb 17.2 was able to specifically detect human β1-AR, stably transfected into HEK cells, by flow cytometry and to induce repolarisation abnormalities and first degree atrioventricular conduction block after passive transfer to naïve mice. To study the structural basis of this cross-reactivity, we determined the crystal structure of the Fab region of the mAb 17.2 alone at 2.31 Å resolution and in complex with the R13 peptide at 1.89 Å resolution. We identified as key contact residues on R13 peptide Glu3, Asp6 and Phe9 as was previously shown by alanine scanning. Additionally, we generated a model of human β1-AR to elucidate the interaction with anti-R13 antibodies. These data provide an understanding of the molecular basis of cross-reactive antibodies induced by chronic infection with Trypanosoma cruzi. PMCID: PMC3206007 Free PMC Article
	PMID: 22069505 [PubMed - indexed for MEDLINE]
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10.	Mol Biochem Parasitol. 2012 Jan;181(1):1-6. Epub 2011 Oct 1. The role of melatonin in parasite biology. Bagnaresi P, Nakabashi M, Thomas AP, Reiter RJ, Garcia CR. Source Departamento de Biofísica, Universidade Federal de São Paulo, São Paulo, Brazil. Abstract Regarded as the circadian hormone in mammals, melatonin is a highly conserved molecule, present in nearly all species. In this review, we discuss the role of this indolamine and its precursors in the cell biology of parasites and the role of the molecule in the physiology of the host. In Plasmodium, melatonin can modulate intracellular concentrations of calcium and cAMP, which in turn can regulate kinase activity and cell cycle. In Trypanosoma infections, modulation of the immune system by melatonin is extremely important in controlling the parasite population. Melatonin also contributes to the inflammatory response to Toxoplasma gondii infection. Thus, there are a number of unique adaptations involving intricate connections between melatonin and the biology of the parasite-host relationship. Copyright © 2011 Elsevier B.V. All rights reserved.
	PMID: 21982826 [PubMed - indexed for MEDLINE]
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