Tuesday, March 20, 2012

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 - 5 of 5

1. Mol Cell Proteomics. 2012 Mar 15. [Epub ahead of print]

Quantitative proteomics reveals that only a subset of the endoplasmic reticulum contributes to the phagosome.

Campbell-Valois FX, Trost M, Chemali M, Dill BD, Laplante A, Duclos S, Sadeghi S, Rondeau C, Morrow IC, Bell C, Hatsuzawa K, Thibault P, Desjardins M.

Source

Institut Pasteur, France;

Abstract

Phagosomes, by killing and degrading pathogens for antigen presentation, are organelles implicated in key aspects of innate and adaptive immunity. While it has been well established that phagosomes consist of membranes from the plasma membrane (PM), endosomes and lysosomes (endo/lyso), the notion that the endoplasmic reticulum (ER) membrane could play an important role in the formation of the phagosome is debated. However, a method to estimate accurately the contribution of potential source organelles and contaminants to the phagosome proteome has been lacking. Herein, we have developed a proteomic approach for objectively quantifying the contribution of various organelles to the early and late phagosomes by comparing these fractions to their total membrane and post-nuclear supernatant of origin in the J774A.1 murine macrophage cell-line. Using quantitative label-free mass spectrometry, the abundance of peptides corresponding to hundreds of proteins was estimated and attributed to one of 5 organelles (e.g. PM, endo/lyso, ER, Golgi and mitochondria). This data in combination with a SILAC method designed to detect potential contaminant sources revealed that the ER is part of the phagosomal membrane and contributes ~20% of the early phagosome proteome. In addition, only a subset of ER proteins is recruited to the phagosome, suggesting that a specific subdomain(s) of the ER might be involved in phagocytosis. Western Blotting and immunofluorescence substantially validated this conclusion; we were able to demonstrate that the fraction of the ER in which the ER marker GFP-KDEL accumulates is excluded from the phagosomes, while that containing the derived SNARE protein mVenus-Stx18 is recruited. These results highlight promising new avenues for the description of the pathogenic mechanisms used by Leishmania, Brucella and Legionella spp., which thrive in ER-rich phagosomes.

PMID: 22427703 [PubMed - as supplied by publisher]
2. J Cell Sci. 2012 Mar 16. [Epub ahead of print]

Polo-like kinase is necessary for flagellum inheritance in Trypanosoma brucei.

Ikeda KN, de Graffenried CL.

Abstract

Polo-like kinases play an important role in a variety of mitotic events in mammalian cells, ranging from centriole separation and chromosome congression to abscission. To fulfill these roles, PLK homologs move to different cellular locations as the cell cycle progresses, starting at the centrosome, progressing to the spindle poles and then the midbody. In the protist parasite Trypanosoma brucei, the single polo-like kinase homolog TbPLK is essential for cytokinesis and is necessary for the correct duplication of a centrin-containing cytoskeletal structure known as the bilobe. We show that TbPLK has a dynamic localization pattern during the cell cycle. The kinase localizes to the basal body, which nucleates the flagellum, and then successively localizes to a series of cytoskeletal structures that regulate the position and attachment of the flagellum to the cell body. The kinase localizes to each of these structures as they are duplicating. TbPLK associates with a specialized set of microtubules, known as the microtubule quartet, which may transport the kinase during its migration. Depletion of TbPLK causes defects in basal body segregation and blocks the duplication of the regulators that position the flagellum, suggesting that its presence on these structures might be necessary for their proper biogenesis. The ability of PLKs to migrate throughout the cell is preserved in T. brucei, but the specific locations to which it targets and functions are geared towards the inheritance of a properly positioned and attached flagellum.

PMID: 22427687 [PubMed - as supplied by publisher]
3. Rheumatology (Oxford). 2012 Mar 15. [Epub ahead of print]

Mucocutaneous leishmaniasis in a patient treated with anti-TNF-α therapy.

Garcia-Gonzalez E, Guidelli GM, Bardelli M, Maggio R.

Source

Department of Clinical Medicine and Immunological Science, Rheumatology Unit, University of Siena, Italy.

PMID: 22427411 [PubMed - as supplied by publisher]
4. Vaccine. 2012 Mar 14. [Epub ahead of print]

The adjuvanticity of Chiococca alba saponins increases with the length and hydrophilicity of their sugar chains.

Nico D, Borges RM, Brandão LM, Feijó DF, Gomes DC, Palatnik M, Rodrigues MM, da Silva AJ, Palatnik-de-Sousa CB.

Source

Departamento de Microbiologia Geral, Instituto de Microbiologia "Paulo de Góes", Universidade Federal do Rio de Janeiro (UFRJ), CP 68040, 21941-902 Rio de Janeiro, Brazil.

Abstract

The saponins of Chiococca alba are triterpene bidesmosides that contain glycidic moieties attached to the C-3 and C-28 carbon of their aglycone. We describe that their adjuvant potential increases in direct relationship to the length and hydrophilicity of the C-28 attached sugar chain which contains: arabinose-rhamnose in the CA2, arabinose-rhamnose-xylose in the CA3X; arabinose-rhamnose-apiose in the CA3 and arabinose-rhamnose-apiose-apiose in the CA4 saponin. The hydrophile/lipophile balance calculated for CA2 was 12.7, for CA3 and CA3X was 15.8 and for CA4 19.9. All saponins were formulated with the FML antigen for mice prophylaxis against visceral leishmaniasis. The immune response was studied using an ELISA-antibody assay and monitoring of the intradermal response (IDR) to Leishmania antigens, the cytokine expression in supernatants and the intracellular staining of in vitro cultured splenocytes. After challenge, significant increases of IgG and IgG2a antibodies were noted only in the CA4 vaccinated mice that showed extended IDR, higher IFN-γ production by CD8+ and TNF-α production by CD4+ T cells, higher TNF-α secretion and the highest reduction of the parasite load (78%). The increases in IDR, CD4-TNF-α, CD8-IFN-γ and CD8-TNF-α by the CA4 vaccine were strong correlates of protection and were significantly correlated to the decrease of parasite load (p=-0.007). Protection generated by the CA4 vaccine was mainly mediated by a CD4+ T cell and a TNF-α driven response with a lower contribution of CD8+ T cells, as confirmed by an in vivo depletion with monoclonal antibodies and by vaccination assays in TNF-α-receptor knock-out mice. Our results confirm that the superiority of the CA4 saponin is related to the higher hydrophilicity of its longer carbohydrate chain. C. alba saponins were non-toxic and only the xylose-containing saponin CA3X was hemolytic (HD(50)=87μg/ml). The increase in sugar units of the saponins is positively correlated to the increase of IDR and to the decrease of parasite load.

Copyright © 2012. Published by Elsevier Ltd.

PMID: 22426042 [PubMed - as supplied by publisher]
5. Int J Parasitol. 2011 Nov;41(13-14):1385-96. Epub 2011 Oct 29.

Multilocus phylogeographical analysis of Trypanosoma (Megatrypanum) genotypes from sympatric cattle and water buffalo populations supports evolutionary host constraint and close phylogenetic relationships with genotypes found in other ruminants.

Garcia HA, Rodrigues AC, Martinkovic F, Minervino AH, Campaner M, Nunes VL, Paiva F, Hamilton PB, Teixeira MM.

Source

Departamento de Parasitologia, Universidade de São Paulo, Instituto de Ciências Biomédicas II, Av. Prof. Lineu Prestes 1374, 05508-900 São Paulo, SP, Brazil.

Abstract

Species of the subgenus Trypanosoma (Megatrypanum) have been reported in cattle and other domestic and wild ruminants worldwide. A previous study in Brazil found at least four genotypes infecting cattle (Bos taurus), but only one in water buffalo (Bubalus bubalis). However, the small number of isolates examined from buffalo, all inhabiting nearby areas, has precluded evaluation of their diversity, host associations and geographical structure. To address these questions, we evaluated the genetic diversity and phylogeographical patterns of 25 isolates from water buffalo and 28 from cattle from four separate locations in Brazil and Venezuela. Multigene phylogenetic analyses of ssrRNA, internal transcribed spacer of rDNA (ITSrDNA), 5SrRNA, glycosomal glyceraldehyde 3-phosphate dehydrogenase (gGAPDH), mitochondrial cytochrome b (Cyt b), spliced leader (SL) and cathepsin L-like (CATL) sequences positioned all isolates from sympatric and allopatric buffalo populations into the highly homogeneous genotype TthIA, while the cattle isolates were assigned to three different genotypes, all distinct from TthIA. Polymorphisms in all of these sequences separated the trypanosomes infecting water buffalo, cattle, sheep, antelope and deer, and suggested that they correspond to separate species. Congruent phylogenies inferred with all genes indicated a predominant clonal structure of the genotypes. The multilocus analysis revealed one monophyletic assemblage formed exclusively by trypanosomes of ruminants, which corresponds to the subgenus T. (Megatrypanum). The high degree of host specificity, evidenced by genotypes exclusive to each ruminant species and lack of genotype shared by different host species, suggested that the evolutionary history of trypanosomes of this subgenus was strongly constrained by their ruminant hosts. However, incongruence between ruminant and trypanosome phylogenies did not support host-parasite co-evolution, indicating that host switches have occurred across ruminants followed by divergences, giving rise to new trypanosome genotypes adapted exclusively to one host species.

Copyright © 2011 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

PMID: 22051399 [PubMed - indexed for MEDLINE]
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