Wednesday, March 25, 2009

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 -6 of 6

1: Int J Immunopathol Pharmacol. 2009 Jan-Mar;22(1):169-74.

Vaccination with Trichinella spirallis antigens increases CD8+ peripheral T cells and enhances the Th2 immune response in Leishmania infantum challenged mice.

Department of Biological Chemistry, School of Medicine, Aristotle University, Thessaloniki, Greece.

In this study we investigate the effect of Trichinella spiralis vaccination on immune responses elicited in BALB/c mice challenged subcutaneously with 0.5 x 10 6 of Leishmania infantum promastigotes. Secretion of specific anti-L. infantum antibodies and changes in the number of CD4+, CD8+ T cell and CD19+ B cells in the peripheral blood were tested for the evaluation of immune responses. Immunization with low amounts of T. spiralis antigens induced depression in anti-Leishmania specific antibodies of the IgG1 isotype, while no changes in the number of CD4+ and CD8+ T cell subpopulations or CD19+ B cells were observed. In contrast, high amounts of T. spiralis antigens induced an enhancement in anti-Leishmania specific antibodies of total IgG and IgG1 isotype, increase of CD8+ T cell number and activation of CD19+ B cells, indicated by the co-expression of CD69 marker. Our results suggest that immunization with a certain dose of T. spiralis antigens in experimentally challenged mice with L. infantum leads to an increase of peripheral CD8+ T cells which are responsible for the control of L. infantum infection, although a simultaneous enhancement in Th2-type of immune response is also observed.

PMID: 19309564 [PubMed - in process]

2: BMC Res Notes. 2009 Mar 23;2(1):46. [Epub ahead of print]Click here to read

Searching for novel cell cycle regulators in Trypanosoma brucei with an RNA interference screen.

ABSTRACT: BACKGROUND: The protozoan parasite, Trypanosoma brucei, is spread by the tsetse fly and causes Human African Trypanosomiasis. Its cell cycle is complex and not fully understood at the molecular level. The T. brucei genome contains over 6000 protein coding genes with >50% having no predicted function. A small scale RNA interference (RNAi) screen was carried out in Trypanosoma brucei to evaluate the prospects for identifying novel cycle regulators. RESULTS: Procyclic form T. brucei were transfected with a genomic RNAi library and 204 clones isolated. However, only 76 RNAi clones were found to target a protein coding gene of potential interest. These clones were screened for defects in proliferation and cell cycle progression following RNAi induction. Sixteen clones exhibited proliferation defects upon RNAi induction, with eight clones displaying potential cell cycle defects. To confirm the phenotypes, new RNAi cell lines were generated and characterised for five genes targeted in these clones. While we confirmed that the targeted genes are essential for proliferation, we were unable to unambiguously classify them as cell cycle regulators. CONCLUSIONS: Our study identified genes essential for proliferation, but did not, as hoped, identify novel cell cycle regulators. Screening of the RNAi library for essential genes was extremely labour-intensive, which was compounded by the suboptimal quality of the library. For such a screening method to be viable for a large scale or genome wide screen, a new, significantly improved RNAi library will be required, and automated phenotyping approaches will need to be incorporated.

PMID: 19309510 [PubMed - as supplied by publisher]

3: Biochem J. 2009 Apr 15;419(2):e1-3.Click here to read

Drug screening by crossing membranes: a novel approach to identification of trypanocides.

Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QT, UK.

Trypanosomes are a group of protozoan parasites that inflict huge health and economic burdens across the globe. The African trypanosome, Trypanosoma brucei, the causative agent of sleeping sickness, has a highly sophisticated mechanism of antigenic variation that facilitates chronic survival in the mammalian host, and also all but eliminates any realistic hope for vaccination-based control. However, trypanosomes are also highly divergent organisms, with many biochemical processes setting them apart from their hosts, and there remains great optimism that these features may be exploited for development of new drugs. Unfortunately, the compounds that are in use at present are decades old and resistance has emerged. The article in this issue of the Biochemical Journal by Patham et al., a joint team from the universities of Pittsburgh and Georgia, represents one approach to exploiting this divergence. The authors of the study have exploited novel aspects of the biochemistry within the system for translocation of nascent polypeptides across the endoplasmic reticulum membrane to identify three compounds that are able to inhibit the process. They then demonstrate that these same compounds are both trypanocidal, but well tolerated by human tissue culture cells. These observations may present interesting new leads in the fight against trypanosomiasis, and potentially identify a new target that can be explored for therapeutic potential.

PMID: 19309311 [PubMed - in process]

4: Parasitol Res. 2009 Mar 24. [Epub ahead of print]Click here to read

Synthetic nonamer peptides derived from insect defensin mediate the killing of African trypanosomes in axenic culture.

National Institute of Agrobiological Sciences, 1-2 Ohwashi, Tsukuba, Ibaraki, 305-8634, Japan, kitani@affrc.go.jp.

Synthetic antimicrobial 9-mer peptides (designated as peptides A and B) designed on the basis of insect defensins and their effects on the growth of African trypanosomes were examined using two isolates of Trypanosoma congolense, IL1180 and IL3338, and two isolates of Trypanosoma brucei brucei, ILTat1.1and GUTat 3.1, under axenic culture conditions. Both peptides inhibited the growth of all bloodstream form (BSF) trypanosomes at 200-400 mug/mL in the complete growth medium, with peptide A being more potent than peptide B. In addition, these peptides exhibited efficient killing at 5-20 mug/mL on BSF trypanosomes suspended in phosphate-buffered saline, whereas procyclic insect forms in the same medium were more refractory to the killing. Electron microscopy revealed that the peptides induced severe defects in the cell membrane integrity of the parasites. The insect defensin-based peptides up to either 200 or 400 mug/mL showed no cell killing or growth inhibition on NIH3T3 murine fibroblasts. The results suggest that the design of suitable synthetic insect defensin-based 9-mer peptides might provide potential novel trypanocidal drugs.

PMID: 19308456 [PubMed - as supplied by publisher]

5: Antimicrob Agents Chemother. 2009 Mar 23. [Epub ahead of print]Click here to read

Intracellular localization of the ABCC proteins of Leishmania and their role in resistance to antimonials.

Centre de Recherche en Infectiologie et Division de Microbiologie, Université Laval, Québec, Canada, G1V 4G2.

The ABCC proteins subfamily is composed of nine members in Leishmania. We report that all of these proteins have an intracellular localization and that the overexpression of at least four members, ABCC3, ABCC4, ABCC5 and ABCC7 can confer resistance to antimonials, the first-line drug against Leishmania.

PMID: 19307364 [PubMed - as supplied by publisher]

6: Trans R Soc Trop Med Hyg. 2009 Jan;103(1):105; author reply 105-6. Epub 2008 Aug 9.Click here to read LinkOut
Comment on:
Trans R Soc Trop Med Hyg. 2008 Apr;102(4):306-7.

Comment on: Diagnosing central nervous system trypanosomiasis: two stage or not to stage.

PMID: 18692858 [PubMed - indexed for MEDLINE]

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