What's new for 'Trypanosomatids' in PubMed

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Sent on Friday, 2010 Sep 10
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 - 9 of 9

1.	Eur J Immunol. 2010 Jul 30. [Epub ahead of print] Murine model of chronic L. (Viannia) panamensis infection: Role of IL-13 in disease. Castilho TM, Goldsmith-Pestana K, Lozano C, Valderrama L, Saravia NG, McMahon-Pratt D. Yale University School of Public Health, New Haven, CT, USA. Abstract Leishmania (Viannia) organisms are the most prevalent etiologic agents of human cutaneous leishmaniasis in the Americas. Nevertheless, our knowledge of the immunological mechanisms exploited by L. (Viannia) organisms remains limited and the mechanisms underlying disease are not well understood. Here, we report the development of a BALB/c mouse model of L. (V.) panamensis infection that is able to reproduce chronic disease, with persistent infection and clinically evident lesions for over 1 year. The immune response of the mouse resembles that found for L. (V.) panamensis-infected patients with chronic and recurrent lesions, presenting a mixed Th1/Th2 response with the presence of TNF-α, IFN-γ, IL-10 and IL-13. Using immunodeficient mice, the critical role for IL-13 and/or IL-4Rα in determining susceptibility to chronic infection was evident. With the induction of healing in the immunodeficient mice, increases in IFN-γ and IL-17 were found, concomitant with parasite control and elimination. Specifically, increases in CD4(+) (but not CD8(+)) T cells producing IFN-γ were observed. These results suggest that IL-13 represents an important target for disease control of L. (V.) panamensis infection. This murine model should be useful to further understand the pathology associated with chronic disease and to develop methods for the treatment and prevention of leishmaniasis caused by L. (Viannia) parasites.
	PMID: 20827674 [PubMed - as supplied by publisher]

2.	Vet Pathol. 2010 Sep 8. [Epub ahead of print] Eight Cases of Feline Cutaneous Leishmaniasis in Texas. Trainor KE, Porter BF, Logan KS, Hoffman RJ, Snowden KF. Abstract Leishmaniasis is a zoonotic disease caused by intracellular Leishmania protozoa that are transmitted by sandflies. The disease occurs in 3 forms: cutaneous, mucocutaneous, and visceral. Cutaneous leishmaniasis has been reported in cats in Europe and South America and in 1 cat from Texas. Leishmania mexicana is endemic in Texas and has been reported to cause cutaneous lesions in humans. This article describes the pathology of 8 biopsy cases of feline cutaneous leishmaniasis presented to the Texas Veterinary Medical Diagnostic Laboratory over a 3.5-year period. The median age of the cats was 3 years; each was presented with nodular, ulcerative lesions on the pinnae and less commonly on the muzzle and periorbital skin. Histologically, the lesions were nodular to diffuse histiocytic dermatitis with numerous amastigotes (2-4 μm) within macrophages and occasionally within the interstitium. Organisms were often contained within round, clear, intracellular vacuoles. In areas of necrosis, organisms were also free within the interstitium. The overlying epidermis was hyperkeratotic, hyperplastic, and often ulcerated. The organisms were not argyrophilic (Gomori methenamine silver), reacted poorly with periodic acid-Schiff reagent, and were inconsistently basophilic with Giemsa. Although not readily visible histologically, kinetoplasts were evident in amastigotes in cytologic preparations. The lesions were similar to those described for cutaneous L. mexicana infection in humans. In 5 of the 8 cats, Leishmania mexicana DNA was amplified from paraffin-embedded tissue by polymerase chain reaction and sequenced.
	PMID: 20826847 [PubMed - as supplied by publisher]

3.	J Biol Chem. 2010 Sep 8. [Epub ahead of print] The dithiol glutaredoxins of African trypanosomes have distinct roles and are closely linked to the unique trypanothione metabolism. Ceylan S, Seidel V, Ziebart N, Berndt C, Dirdjaja N, Krauth-Siegel RL. Centre of Biochemistry of Heidelberg University, Germany; Abstract Trypanosoma brucei, the causative agent of African sleeping sickness, possesses two dithiol glutaredoxins (Grx1 and Grx2). Grx1 occurs in the cytosol and catalyzes protein deglutathionylations with kcat/Km-values of up to 2 x 105 M-1s-1. It accelerates the reduction of ribonucleotide reductase by trypanothione although less efficiently than the parasite tryparedoxin and has low insulin disulfide reductase activity. Despite its classical CPYC active site, Grx1 forms dimeric iron sulphur complexes with GSH, glutathionylspermidine or trypanothione as non-protein ligands. Thus, contrary to the generally accepted assumption, replacement of the Pro is not a prerequisite for cluster formation. T. brucei Grx2 shows an unusual CQFC active site and orthologues occur exclusively in trypanosomatids. Grx2 is enriched in mitoplasts and fractionated digitonin lysis resulted in a co-elution with cytochrome c suggesting a localisation in the mitochondrial intermembrane space. Grx2 catalyzes the reduction of insulin disulfide but not of ribonucleotide reductase and exerts 10-fold lower deglutathionylation activity than Grx1. RNA interference against Grx2 caused a growth retardation of procyclic cells consistent with an essential role. Grx1 and Grx2 are constitutively expressed with cellular concentrations of about 2 μM and 200 nM, respectively, in both the mammalian bloodstream and insect procyclic forms. Trypanothione reduces the disulfide form of both proteins with apparent rate constants that are three orders of magnitude higher than those with glutathione. Grx1, and less efficiently also Grx2, catalyse the reduction of GSSG by trypanothione. Thus, the Grxs play exclusive roles in the trypanothione-based thiol redox metabolism of African trypanosomes.
	PMID: 20826822 [PubMed - as supplied by publisher]

4.	J Immunol. 2010 Sep 8. [Epub ahead of print] Leishmania donovani Promastigotes Evade the Antimicrobial Activity of Neutrophil Extracellular Traps. Gabriel C, McMaster WR, Girard D, Descoteaux A. Institut National de la Recherche Scientifique, Institut Armand-Frappier; Abstract Upon their recruitment to a site of infection and their subsequent activation, neutrophils release DNA and a subset of their granule content to form filamentous structures, known as neutrophil extracellular traps, which capture and kill microorganisms. In this study, we show that Leishmania promastigotes induced the rapid release of neutrophil extracellular traps from human neutrophils and were trapped by these structures. The use of Leishmania mutants defective in the biosynthesis of either lipophosphoglycan or GP63 revealed that these two major surface promastigote virulence determinants were not responsible for inducing the release of the surface protease neutrophil extracellular traps. We also demonstrate that this induction was independent of superoxide production by neutrophils. Finally, in contrast to wild-type Leishmania donovani promastigotes, mutants defective in lipophosphoglycan biosynthesis were highly susceptible to the antimicrobial activity of neutrophil extracellular traps. Altogether, our data suggest that neutrophil extracellular traps may contribute to the containment of L. donovani promastigotes at the site of inoculation, thereby facilitating their uptake by mononuclear phagocytes.
	PMID: 20826753 [PubMed - as supplied by publisher]

5.	J Cell Sci. 2010 Sep 7. [Epub ahead of print] Developmental regulation and extracellular release of a VSG expression-site-associated gene product from Trypanosoma brucei bloodstream forms. Barnwell EM, van Deursen FJ, Jeacock L, Smith KA, Maizels RM, Acosta-Serrano A, Matthews K. Abstract Trypanosomes evade host immunity by exchanging variant surface glycoprotein (VSG) coats. VSG genes are transcribed from telomeric expression sites, which contain a diverse family of expression-site-associated genes (ESAGs). We have discovered that the mRNAs for one ESAG family, ESAG9, are strongly developmentally regulated, being enriched in stumpy forms, a life-cycle stage in the mammalian bloodstream that is important for the maintenance of chronic parasite infections and for tsetse transmission. ESAG9 gene sequences are highly diverse in the genome and encode proteins with weak similarity to the massively diverse MASP proteins in Trypanosoma cruzi. We demonstrate that ESAG9 proteins are modified by N-glycosylation and can be shed to the external milieu, this being dependent upon coexpression with at least one other family member. The expression profile and extracellular release of ESAG9 proteins represents a novel and unexpected aspect of the transmission biology of trypanosomes in their mammalian host. We suggest that these molecules might interact with the external environment, with possible implications for infection chronicity or parasite transmission.
	PMID: 20826456 [PubMed - as supplied by publisher]

6.	Biochemistry. 2010 Sep 8. [Epub ahead of print] STRUCTURE AND MECHANISM OF THE 6-OXOPURINE NUCLEOSIDASE FROM TRYPANOSOMA BRUCEI BRUCEI. Vandemeulebroucke A, Minici C, Bruno I, Muzzolini L, Tornaghi P, Parkin DW, Versées W, Steyaert J, Degano M. Abstract Trypanosomes are purine-auxotrophic parasites that depend upon nucleoside hydrolase (NH) activity to salvage nitrogenous bases necessary for nucleic acid and cofactor synthesis. Non-specific and purine-specific NHs have been widely studied, yet little is known about the 6-oxopurine-specific isozymes, although postulated to play a primary role in the catabolism of exogenously-derived nucleosides. Here, we report the first functional and structural characterization of the inosine-guanosine-specific NH from Trypanosoma brucei brucei. The enzyme shows near diffusion-limited efficiency coupled to a clear specificity for 6-oxo purine nucleosides achieved through a catalytic selection of these substrates. Pre-steady-state kinetic analysis reveals ordered product release, and a rate-limiting structural rearrangement that is associated with the release of the product, ribose. The crystal structure to 2.5-Å resolution of this trypanosomal NH reveals distinctive features compared to both purine and pyrimidine-specific isozymes in the framework of the conserved and versatile NH fold. Nanomolar iminoribitol-based inhibitors identified in this study represent important lead compounds for the development of novel therapeutic strategies against trypanosomal diseases.
	PMID: 20825170 [PubMed - as supplied by publisher]

7.	Trends Parasitol. 2010 May;26(5):225-9. Epub 2010 Mar 6. Sequence-based functional annotation: what if most of the genes are unique to a genome? Salavati R, Najafabadi HS. Institute of Parasitology, McGill University, 21,111 Lakeshore Road, Ste. Anne de Bellevue, Montreal, Quebec H9X3V9, Canada. reza.salavati@mcgill.ca <reza.salavati@mcgill.ca> Abstract The genomes of trypanosomatids are distantly related to other eukaryotes, with significant numbers of hypothetical or conserved hypothetical trypanosomatid-specific genes, whose functions cannot be determined using homology-dependent annotation methods. Here, we describe homology-independent methods to infer biological functions of genes based solely on their sequences. These approaches are not limited to trypanosomatid genomes and provide grounds for analysis of genomes of Plasmodium falciparum and other parasites associated with neglected tropical diseases. A critical evaluation of the current state of annotation of parasitic genomes endorses the need to exploit homology-independent computational methods, which can identify protein functions, potentially including essential genes, and provide a plethora of valuable information on interaction networks and regulatory elements.
	PMID: 20211583 [PubMed - indexed for MEDLINE]
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8.	Res Vet Sci. 2010 Aug;89(1):98-103. Epub 2010 Mar 3. DHEA and testosterone therapies in Trypanosoma cruzi-infected rats are associate d with thymic changes. Filipin Mdel V, Caetano LC, Brazão V, Santello FH, Toldo MP, do Prado JC Jr. Department of Clinical Analysis, Toxicology and Bromatology, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil. Av. do Café s/n, 14040-903 Ribeirão Preto, SP, Brazil. Abstract The ability of the gonadal hormones to influence diverse immunological functions during the course of several infections has been extensively studied in the latest decades. Testosterone has a suppressive effect on immune response of vertebrates and increases susceptibility toward numerous parasitic diseases. Dehydroepiandrosterone is an abundant steroid hormone secreted by the human adrenal cortex and it is considered potent immune-activator. In this paper, it was examined the effects of DHEA and testosterone supplementation in the thymic atrophy in rats infected with Trypanosoma cruzi, by comparing blood parasitism, thymocyte proliferation, TNF-alpha and IL-12 levels. Our data point in the direction that DHEA treatment triggered enhanced thymocyte proliferation as compared to its infected counterparts and reduced production of TNF-alpha during the acute phase of infection. Oppositely, the lowest values for cells proliferation and IL-12 concentrations were reached in testosterone-supplied animals. The combined treatment testosterone and DHEA improves the effectiveness of the host's immune response, reducing blood parasites and the immunosuppressive effects of male androgens besides increasing IL-12 concentrations and decreasing TNF-alpha levels.
	PMID: 20202657 [PubMed - indexed for MEDLINE]
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9.	Res Vet Sci. 2010 Aug;89(1):27-35. Epub 2010 Feb 11. The impact of concomitant infections by Trypanosoma cruzi and intestinal helminths on the health of wild golden and golden-headed lion tamarins. Monteiro RV, Dietz JM, Jansen AM. Instituto Oswaldo Cruz, FIOCRUZ, Av. Brasil, 4365, Rio de Janeiro, RJ 21040-360, Brazil. rvmonteiro@unb.br Abstract A 4-year longitudinal epidemiological study was carried out to evaluate the effect of infection by Trypanosoma cruzi and three intestinal helminth species on the health of golden and golden-headed lion tamarins. We evaluated health using analysis of blood counts, serum proteins, electrophoretograms, electrocardiograms and a health ranking based on physiological parameters. Among the helminths, Trichostrongylidae was demonstrated as the most pathogenic, followed by Prosthenorchis sp.; concomitant infection by Spiruridae may exacerbate the negative effects of the other two helminths. T. cruzi infection was not highly detrimental to the health of the study animals and was correlated with increased resilience to helminths. Tamarins younger than 1-year of age or older than 4-years had lower health condition. Golden-headed lion tamarins were in lower health condition because of higher parasitic prevalence. Our data suggest that when parasite community pathogenicity and prevalence are high, natural selection will allow survival only of lion tamarins in the best health condition.
	PMID: 20149919 [PubMed - indexed for MEDLINE]
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