Thursday, February 4, 2010

What's new for 'Trypanosomatids' in PubMed

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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 19

1. Phytother Res. 2010 Feb 1. [Epub ahead of print]

In Vitro activities of plant extracts from Saudi Arabia against malaria, leishmaniasis, sleeping sickness and Chagas disease.

Abdel-Sattar E, Maes L, Salama MM.

Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

The in vitro activity of the methanol extracts of 51 plants randomly collected from the Kingdom of Saudi Arabia and some of their fractions (petroleum ether, chloroform, ethyl acetate and aqueous) were evaluated against Plasmodium falciparum, Trypanosoma brucei brucei, T. cruzi and Leishmania infantum, as well as toxicity against MRC-5 fibroblast cells. Ten crude methanolic extracts that demonstrated potent and adequately selective antiprotozoal activity were subjected to solvent fractionation using petroleum ether, ethyl acetate and chloroform. Only three samples showed promising antiprotozoal activity. Argemone ochroleuca (CHCl(3) fraction) showed pronounced activity against P. falciparum(GHA) (IC(50) 0.32 mug/mL) and T. cruzi (IC(50) 0.30 mug/mL) with low cytotoxicity against MRC-5 cells (CC(50) 11.6 mug/mL). Capparis spinosa (EtOAc fraction) showed pronounced activity against P. falciparum(GHA) with an IC(50) 0.50 mug/mL in the absence of toxicity against MRC-5 cell line (CC(50) > 30 mug/mL). Heliotropium curassavicum (CHCl(3) fraction) showed similar activity against P. falciparum (IC(50) 0.65 mug/mL; MRC-5 CC(50) > 30 mug /mL). These three extracts will be subjected for further extensive studies to isolate and identify their active constituents. Copyright (c) 2010 John Wiley & Sons, Ltd.

PMID: 20127723 [PubMed - as supplied by publisher]
2. Parasitol Res. 2010 Feb 3. [Epub ahead of print]

Detection of Leishmania infantum in Rhipicephalus sanguineus ticks from Brazil and Italy.

Dantas-Torres F, Lorusso V, Testini G, de Paiva-Cavalcanti M, Figueredo LA, Stanneck D, Mencke N, Brandão-Filho SP, Alves LC, Otranto D.

Dipartimento di Sanità Pubblica e Zootecnia, Università degli Studi di Bari, Valenzano, BA, Italy, f.dantastorres@veterinaria.uniba.it.

Canine leishmaniosis is a widespread disease caused by Leishmania parasites, which are transmitted by phlebotomine sand flies. However, in some areas where canine leishmaniosis is endemic, but the primary vectors have not been found, ticks have been suspected to play a role in transmitting the infection. Herewith, we report the detection of Leishmania infantum kinetoplast minicircle DNA (kDNA) in ticks collected from naturally infected dogs living in rural areas of Southern Italy (site A) and Northeastern Brazil (site B). Between March and October 2007, ticks were collected from 26 dogs positive to anti-Leishmania antibodies (one from site A and 25 from site B) and either placed directly into vials containing 70% ethanol or maintained alive for identification and subsequent dissection. All the 95 ticks collected were morphologically identified as Rhipicephalus sanguineus. After identification, their genomic DNA was extracted (either individually or in pools) and processed by polymerase chain reaction (PCR) for the detection of L. infantum kDNA. Two pools of salivary glands from ticks (one from five females and other from five males) found on a dog from site A and tested by a conventional PCR were positive. Amplicon sequencing confirmed the identity of the parasite. In addition, nine (12.3%) out of the 73 ticks found on dogs from site B and tested by a real-time PCR were positive, with a low parasite load (less than 1 parasite/ml). The retrieval of L. infantum kDNA in salivary glands of R. sanguineus ticks has been here reported for the first time. Therefore, further studies are needed to assess the competence of ticks as vectors of Leishmania parasites from dog to dog.

PMID: 20127362 [PubMed - as supplied by publisher]
3. PLoS Pathog. 2010 Jan 29;6(1):e1000739.

Social motility in african trypanosomes.

Oberholzer M, Lopez MA, McLelland BT, Hill KL.

Department of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, California, United States of America.

African trypanosomes are devastating human and animal pathogens that cause significant human mortality and limit economic development in sub-Saharan Africa. Studies of trypanosome biology generally consider these protozoan parasites as individual cells in suspension cultures or in animal models of infection. Here we report that the procyclic form of the African trypanosome Trypanosoma brucei engages in social behavior when cultivated on semisolid agarose surfaces. This behavior is characterized by trypanosomes assembling into multicellular communities that engage in polarized migrations across the agarose surface and cooperate to divert their movements in response to external signals. These cooperative movements are flagellum-mediated, since they do not occur in trypanin knockdown parasites that lack normal flagellum motility. We term this behavior social motility based on features shared with social motility and other types of surface-induced social behavior in bacteria. Social motility represents a novel and unexpected aspect of trypanosome biology and offers new paradigms for considering host-parasite interactions.

PMID: 20126443 [PubMed - in process]
4. PLoS Negl Trop Dis. 2010 Feb 2;4(2):e589.

Thrichomys laurentius (Rodentia; Echimyidae) as a Putative Reser voir of Leishmania infantum and L. braziliensis: Patterns of Experimental Infection.

Roque AL, Cupolillo E, Marchevsky RS, Jansen AM.

Laboratory of Tripanosomatid Biology, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil.

The importance of the genus Thrichomys in the retention of infection and transmission of Leishmania species is supported by previous studies that describe an ancient interaction between caviomorphs and trypanosomatids and report the natural infection of Thrichomys spp. Moreover, these rodents are widely dispersed in Brazil and recognized as important hosts of other tripanosomatids. Our main purpose was to evaluate the putative role of Thrichomys laurentius in the retention of infection and amplification of the transmission cycle of Leishmania infantum and L. braziliensis. Male and female T. laurentius (n = 24) born in captivity were evaluated for the retention of infection with these Leishmania species and followed up by parasitological, serological, hematological, biochemical, histological, and molecular assays for 3, 6, 9, or 12 months post infection (mpi). T. laurentius showed its competence as maintenance host for the two inoculated Leishmania species. Four aspects should be highlighted: (i) re-isolation of parasites 12 mpi; (ii) the low parasitic burden displayed by T. laurentius tissues; (iii) the early onset and maintenance of humoral response, and (iv) the similar pattern of infection by the two Leishmania species. Both Leishmania species demonstrated the ability to invade and maintain itself in viscera and skin of T. laurentius, and no rodent displayed any lesion, histological changes, or clinical evidence of infection. We also wish to point out the irrelevance of the adjective dermotropic or viscerotropic to qualify L. braziliensis and L. infantum, respectively, when these species are hosted by nonhuman hosts. Our data suggest that T. laurentius may act at least as a maintenance host of both tested Leishmania species since it maintained long-lasting infections. Moreover, it cannot be discarded that Leishmania spp. infection in free-ranging T. laurentius could result in higher parasite burden due the more stressing conditions in the wild. Therefore the tissular parasitism of the skin, infectiveness to the vector, and amplification of the transmission cycle of both Leishmania species could be expected.

PMID: 20126407 [PubMed - in process]
5. PLoS Negl Trop Dis. 2010 Jan 26;4(1):e590.

A CATT Negative Result after Treatment for Human African Trypanosomiasis Is No Indication for Cure.

Lejon V, Ngoyi DM, Boelaert M, Büscher P.

Department of Parasitology, Institute of Tropical Medicine, Antwerp, Belgium.

BACKGROUND: Cure after treatment for human African trypanosomiasis (HAT) is assessed by examination of the cerebrospinal fluid every 6 months, for a total period of 2 years. So far, no markers for cure or treatment failure have been identified in blood. Trypanosome-specific antibodies are detectable in blood by the Card Agglutination Test for Trypanosomiasis (CATT). We studied the value of a normalising, negative post-treatment CATT result in treated Trypanosoma brucei (T.b.) gambiense sleeping sickness patients as a marker of cure. METHODOLOGY/PRINCIPAL FINDINGS: The CATT/T.b. gambiense was performed on serum of a cohort of 360 T.b. gambiense patients, consisting of 242 primary and 118 retreatment cases. The CATT results during 2 years of post-treatment follow-up were studied in function of cure or treatment failure. At inclusion, sensitivity of CATT was 98% (234/238) in primary cases and only 78% (91/117) in retreatment cases. After treatment, the CATT titre decreased both in cured patients and in patients experiencing treatment failure. CONCLUSIONS/SIGNIFICANCE: Though CATT is a good test to detect HAT in primary cases, a normalising or negative CATT result after treatment for HAT does not indicate cure, therefore CATT cannot be used to monitor treatment outcome.

PMID: 20126270 [PubMed - in process]
6. PLoS Negl Trop Dis. 2010 Jan 26;4(1):e587.

Effect of Village-wide Use of Long-Lasting Insecticidal Nets on Visceral Leishmaniasis Vectors in India and Nepal: A Cluster Randomized Trial.

Picado A, Das ML, Kumar V, Kesari S, Dinesh DS, Roy L, Rijal S, Das P, Rowland M, Sundar S, Coosemans M, Boelaert M, Davies CR.

London School of Hygiene and Tropical Medicine, London, United Kingdom.

BACKGROUND: Visceral leishmaniasis (VL) control in the Indian subcontinent is currently based on case detection and treatment, and on vector control using indoor residual spraying (IRS). The use of long-lasting insecticidal nets (LN) has been postulated as an alternative or complement to IRS. Here we tested the impact of comprehensive distribution of LN on the density of Phlebotomus argentipes in VL-endemic villages. METHODS: A cluster-randomized controlled trial with household P. argentipes density as outcome was designed. Twelve clusters from an ongoing LN clinical trial-three intervention and three control clusters in both India and Nepal-were selected on the basis of accessibility and VL incidence. Ten houses per cluster selected on the basis of high pre-intervention P. argentipes density were monitored monthly for 12 months after distribution of LN using CDC light traps (LT) and mouth aspiration methods. Ten cattle sheds per cluster were also monitored by aspiration. FINDINGS: A random effect linear regression model showed that the cluster-wide distribution of LNs significantly reduced the P. argentipes density/house by 24.9% (95% CI 1.80%-42.5%) as measured by means of LTs. INTERPRETATION: The ongoing clinical trial, designed to measure the impact of LNs on VL incidence, will confirm whether LNs should be adopted as a control strategy in the regional VL elimination programs. The entomological evidence described here provides some evidence that LNs could be usefully deployed as part of the VL control program. TRIAL REGISTRATION: ClinicalTrials.gov CT-2005-015374.

PMID: 20126269 [PubMed - in process]
7. PLoS Negl Trop Dis. 2010 Jan 26;4(1):e586.

Characterization of a Subunit of the Outer Dynein Arm Docking Complex Necessary for Correct Flagellar Assembly in Leishmania donovani.

Harder S, Thiel M, Clos J, Bruchhaus I.

Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.

BACKGROUND: In order to proceed through their life cycle, Leishmania parasites switch between sandflies and mammals. The flagellated promastigote cells transmitted by the insect vector are phagocytized by macrophages within the mammalian host and convert into the amastigote stage, which possesses a rudimentary flagellum only. During an earlier proteomic study of the stage differentiation of the parasite we identified a component of the outer dynein arm docking complex, a structure of the flagellar axoneme. The 70 kDa subunit of the outer dynein arm docking complex consists of three subunits altogether and is essential for the assembly of the outer dynein arm onto the doublet microtubule of the flagella. According to the nomenclature of the well-studied Chlamydomonas reinhardtii complex we named the Leishmania protein LdDC2. METHODOLOGY/PRINCIPAL FINDINGS: This study features a characterization of the protein over the life cycle of the parasite. It is synthesized exclusively in the promastigote stage and localizes to the flagellum. Gene replacement mutants of lddc2 show reduced growth rates and diminished flagellar length. Additionally, the normally spindle-shaped promastigote parasites reveal a more spherical cell shape giving them an amastigote-like appearance. The mutants lose their motility and wiggle in place. Ultrastructural analyses reveal that the outer dynein arm is missing. Furthermore, expression of the amastigote-specific A2 gene family was detected in the deletion mutants in the absence of a stage conversion stimulus. In vitro infectivity is slightly increased in the mutant cell line compared to wild-type Leishmania donovani parasites. CONCLUSIONS/SIGNIFICANCE: Our results indicate that the correct assembly of the flagellum has a great influence on the investigated characteristics of Leishmania parasites. The lack of a single flagellar protein causes an aberrant morphology, impaired growth and altered infectiousness of the parasite.

PMID: 20126266 [PubMed - in process]
8. PLoS Med. 2010 Jan 26;7(1):e1000206.

Microscopy quality control in médecins sans frontières programs in resource-limited settings.

Klarkowski DB, Orozco JD.

Médecins Sans Frontières-Operational Center Amsterdam, Amsterdam, The Netherlands.

Derryck Klarkowski and Daniel Orozco describe the Médecins Sans Frontières program for monitoring the quality of microscopy for malaria, pulmonary tuberculosis, and leishmaniasis.

PMID: 20126251 [PubMed - in process]
9. Philos Trans R Soc Lond B Biol Sci. 2010 Mar 12;365(1541):819-30.

Autophagy in unicellular eukaryotes.

Kiel JA.

Molecular Cell Biology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, , PO Box 14, 9750 Haren, The Netherlands.

Cells need a constant supply of precursors to enable the production of macromolecules to sustain growth and survival. Unlike metazoans, unicellular eukaryotes depend exclusively on the extracellular medium for this supply. When environmental nutrients become depleted, existing cytoplasmic components will be catabolized by (macro)autophagy in order to re-use building blocks and to support ATP production. In many cases, autophagy takes care of cellular housekeeping to sustain cellular viability. Autophagy encompasses a multitude of related and often highly specific processes that are implicated in both biogenetic and catabolic processes. Recent data indicate that in some unicellular eukaryotes that undergo profound differentiation during their life cycle (e.g. kinetoplastid parasites and amoebes), autophagy is essential for the developmental change that allows the cell to adapt to a new host or form spores. This review summarizes the knowledge on the molecular mechanisms of autophagy as well as the cytoplasm-to-vacuole-targeting pathway, pexophagy, mitophagy, ER-phagy, ribophagy and piecemeal microautophagy of the nucleus, all highly selective forms of autophagy that have first been uncovered in yeast species. Additionally, a detailed analysis will be presented on the state of knowledge on autophagy in non-yeast unicellular eukaryotes with emphasis on the role of this process in differentiation.

PMID: 20124347 [PubMed - in process]
10. J Biol Chem. 2010 Feb 1. [Epub ahead of print]

The allosteric mechanism of pryuvate kinase from Leishmania mexicana: a rock and lock model.

Morgan HP, McNae IW, Nowicki MW, Hannaert V, Michels PA, Fothergill-Gilmore LA, Walkinshaw MD.

Edinburgh University, United Kingdom;

Allosteric regulation provides a rate management system for enzymes involved in many cellular processes. Ligand-controlled regulation is easily recognisable, but the underlying molecular mechanisms have remained elusive. We have obtained the first complete series of allosteric structures, in all possible ligated states, for the tetrameric enzyme, pyruvate kinase. The transition between inactive T-state and active R-state is accompanied by a simple symmetrical 6o rigid-body rocking motion of the A- and C-domain cores in each of the four subunits. However, formation of the R-state in this way is only part of the mechanism; eight essential salt-bridge locks which form across the C-C interface provide tetramer rigidity with a coupled 7-fold increase in rate. The results presented here illustrate how conformational changes coupled with effector binding correlate with loss of flexibility and increase in thermal stability providing a general mechanism for allosteric control.

PMID: 20123988 [PubMed - as supplied by publisher]

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