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Sent on Tuesday, 2009 Mar 24Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
- 1: Eukaryot Cell. 2009 Mar 20. [Epub ahead of print]
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Ornithine decarboxylase and spermidine synthase RNAi-mediated gene silencing in Trypanosoma brucei provides insight into the regulation of polyamine biosynthesis.
Dept. of Pharmacology, University of Texas Southwestern Medical Center, 6001 Forest Park Rd, Dallas, TX 75390-9041; and Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
Polyamine biosynthesis is a drug target for the treatment of African sleeping sickness, however mechanisms regulating the pathway in Trypanosoma brucei are not well understood. Recently we showed that RNAi-mediated gene silencing or inhibition of S-adenosylmethionine decarboxylase (AdoMetDC) led to upregulation of the AdoMetDC activator, prozyme, and ornithine decarboxylase (ODC) proteins. To determine if this regulatory response is specific to AdoMetDC we studied the effects of RNAi-induced silencing of the spermidine synthase (SpdSyn) and ODC genes in bloodstream form T. brucei. Knockdown of either gene product led to depletion of polyamine and trypanothione pools, and to cell death. Decarboxylated AdoMet levels were elevated, while AdoMet was not affected. There was no significant effect on protein levels of other polyamine pathway enzymes. Treatment of parasites with the ODC inhibitor alpha-difluoromethylornithine (DFMO) gave similar results to those observed for ODC knockdown. Thus the cellular response to loss of AdoMetDC activity is distinctive, suggesting that AdoMetDC activity controls expression levels of the other spermidine biosynthetic enzymes. ODC RNAi-mediated cell death occurred more rapidly than for SpdSyn. Further the ODC RNAi cells were rescued by putrescine, but not spermidine, suggesting that depletion of both putrescine and spermidine is more detrimental than depletion of spermidine alone. This finding may contribute to the effectiveness of ODC as a target for the treatment of African sleeping sickness, thus providing important insight into the mechanism of action of a key anti-trypanosomal agent.
PMID: 19304951 [PubMed - as supplied by publisher]
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Related Articles
- Regulated expression of an essential allosteric activator of polyamine biosynthesis in African trypanosomes. [PLoS Pathog. 2008]
- Antitrypanosomal effects of polyamine biosynthesis inhibitors correlate with increases in Trypanosoma brucei brucei S-adenosyl-L-methionine. [Biochem J. 1991]
- Effects of S-adenosyl-1,8-diamino-3-thio-octane and S-methyl-5'-methylthioadenosine on polyamine synthesis in Ehrlich ascites-tumour cells. [Biochem J. 1989]
- ReviewTargeting the polyamine biosynthetic enzymes: a promising approach to therapy of African sleeping sickness, Chagas' disease, and leishmaniasis. [Amino Acids. 2007]
- ReviewTranslational regulation of ornithine decarboxylase and other enzymes of the polyamine pathway. [Int J Biochem Cell Biol. 1999]
- 2: Exp Parasitol. 2009 Mar 19. [Epub ahead of print]
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Leishmania (Viannia) panamensis: An in vitro assay using the expression of GFP for screening of antileishmanial drug.
Programa de Estudio y Control de Enfermedades Tropicales-PECET, Universidad de Antioquia, Calle 62 No 52-59, Lab. 632, Medelli n, Colombia.
Promastigotes of Leishmania (Viannia) panamensis were successfully transfected with p6.5-egfp to express green fluorescent protein. The transfectants remained infective to macrophages, providing an in vitro model for screening antileishmanial drugs. This was demonstrated by flow cytometry of macrophage-associated GFP after exposure of infected cultures to known anti-leishmanial drugs, i. e. amphotericin B and glucantime(R). Fluorescence of GFP diminished progressively from infected cells with increasing drug concentrations used in both cases. The availability of this fluorescent assay for infection of macrophages by L. (V.) panamensis facilitates drug discovery program for the Viannia species, which differ significantly from those of the Leishmania subgenus.
PMID: 19303871 [PubMed - as supplied by publisher]
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Related Articles
- A microplate assay for Leishmania amazonensis promastigotes expressing multimeric green fluorescent protein. [Parasitol Res. 2003]
- Permissiveness of human monocytes and monocyte-derived macrophages to infection by promastigotes of Leishmania (Viannia) panamensis. [J Parasitol. 1998]
- Applications of recombinant Leishmania amazonensis expressing egfp or the beta-galactosidase gene for drug screening and histopathological analysis. [Exp Anim. 2003]
- Flow cytometry, a useful tool for detecting the lethal effect of pentamidine on Leishmania viannia complex promastigote forms. [Pharmacol Res. 2001]
- ReviewLeishmania (Viannia) lainsoni (Kinetoplastida: Trypanosomatidae), a divergent Leishmania of the Viannia subgenus--a mini review. [Mem Inst Oswaldo Cruz. 2005]
- 3: Phytomedicine. 2009 Mar 19. [Epub ahead of print]
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Nuphar lutea: In vitro anti-leishmanial activity against Leishmania major promastigotes and amastigotes.
The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Israel; Laboratory of Parasitology, Soroka University Medical Center, Beer Sheva, Israel.
Several anti-leishmanial drugs of choice are of plant origin. Many of the available drugs against the disease are toxic and in certain cases parasite drug resistance is developed. The development of new compounds is urgently required. AIMS OF THE STUDY: To determine the leishmanicidal activity of the Nuphar lutea plant extract against Leishmania major in vitro. MATERIALS AND METHODS: The leishmanicidal activity of methanolic plant extract against L. major free living promastigotes and intracellular amastigotes was evaluated, using microscopic examinations and the enzymatic XTT assay. RESULTS: Methanolic extract of N. lutea was highly effective against both Leishmania promastigotes and L. amastigotes (IC(50)=2+/-0.12mug/ml; ID(50)=0.65+/-0.023mug/ml; LD(50)=2.1+/-0.096mug/ml, STI=3.23). The extract at 1.25mug/ml totally eliminated the intracellular parasites within 3 days of treatment. Also, a synergistic anti-leishmanial activity was demonstrated with N. lutea extract combined with the anti-leishmanial drug - paromomycin. The partially purified N. lutea active component was found to be a thermo-stable alkaloid(s) with no electrical charge and is resistant to boiling and to methanol, dichloromethane and xylene treatment. CONCLUSIONS: The present study suggests that N. lutea might be a potential source of anti-leishmanial compounds.
PMID: 19303752 [PubMed - as supplied by publisher]
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Related Articles
- In vitro and in vivo anti-leishmanial activity of chlorpromazine alone and combined with N-meglumine antimonate. [Ann Trop Med Parasitol. 1986]
- Chemotherapeutic activity of rifampicin on leishmanial amastigotes and promastigotes in vitro. [Isr J Med Sci. 1983]
- Anti-leishmanial activity of alkaloidal extract from Aspidosperma ramiflorum. [Mem Inst Oswaldo Cruz. 2004]
- The in vitro activity of Vernonia amygdalina on Leishmania aethiopica. [Ethiop Med J. 1993]
- Review[Nitric oxide and anti-protozoan chemotherapy] [Parassitologia. 2004]
- 4: Exp Parasitol. 2009 Mar 17. [Epub ahead of print]
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Prodigiosin is not a determinant factor in lysis of Leishmania (Viannia) braziliensis after interaction with Serratia marcescens D-mannose sensitive fimbriae.
Laboratório de Bioqui mica e Fisiologia de Insetos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Avenida Brasil 4354, Manguinhos, CEP 21045-900, Rio de Janeiro, RJ, Brazil.
In this paper the lytic activity of two variants of Serratia marcescens against promastigotes of Leishmania braziliensis was studied. In vitro assays showed that S. marcescens variant SM365 lyses L. braziliensis promastigotes, while the variant DB11 did not. Scanning electron microscopy (SEM) revealed that S. marcescens SM365 adheres to all cellular body and flagellum of the parasite. Several filamentous structures were formed and identified as biofilms. After 120 minutes incubation, they connect the protozoan to the developing bacterial clusters. SEM also demonstrated that bacteria, adhered onto L. braziliensis promastigote surface, formed small filamentous structures which apparently penetrates into the parasite membrane. D-mannose protects L. braziliensis against the S. marcescens SM365 lytic effect in a dose dependent manner. SM365 variant pre cultivated at 37(o)C did not synthesize prodigiosin although the adherence and lysis of L. braziliensis were similar to the effect observed with bacteria cultivated at 28(o)C, which produce high concentrations of prodigiosin. Thus, we suggest that prodigiosin is not involved in the lysis of promastigotes and that adherence promoted by bacterial mannose-sensitive (MS) fimbriae is a determinant factor in the lysis of L. braziliensis by S. marcescens SM365.
PMID: 19303010 [PubMed - as supplied by publisher]
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Related Articles
- Leishmania (Leishmania) chagasi interactions with Serratia marcescens: ultrastructural studies, lysis and carbohydrate effects. [Exp Parasitol. 2008]
- Trypanosoma cruzi: ultrastructural studies of adhesion, lysis and biofilm formation by Serratia marcescens. [Exp Parasitol. 2007]
- Isolation of Serratia marcescens in the midgut of Rhodnius prolixus: impact on the establishment of the parasite Trypanosoma cruzi in the vector. [Exp Parasitol. 2004]
- ReviewProdigiosin-like pigments. [CRC Crit Rev Microbiol. 1975]
- ReviewSerratia marcescens. [J Med Microbiol. 1997]
- 5: BMC Genomics. 2009 Mar 20;10(1):119. [Epub ahead of print]
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Transcriptional signatures of BALB/c mouse macrophages housing multiplying Leishmania amazonensis amastigotes.
ABSTRACT: BACKGROUND: Mammal macrophages display a wide range of functions which contribute to surveying and maintaining tissue integrity. One such function is phagocytosis, a process known to be subverted by parasites like Leishmania (L). Indeed, the intracellular development of L. amazonensis amastigote relies on the biogenesis and dynamic remodelling of a phagolysosome, termed the parasitophorous vacuole, primarily within dermal macrophages. RESULTS: Using BALB/c mouse bone marrow-derived macrophages loaded or not with amastigotes, we analyzed the transcriptional signatures of macrophages 24h later, when the amastigote population was growing. Total RNA from macrophage cultures were processed and hybridized onto Affymetrix Mouse430_2 GeneChips(R), and some transcripts were also analyzed by Real-Time quantitative PCR (RTQPCR). A total of 1,248 probe-sets showed significant differential expression. Comparable fold-change values were obtained between the Affymetrix technology and the RTQPCR method. Ingenuity Pathway Analysis software(R) pinpointed the up-regulation of the sterol biosynthesis pathway (p-value = 1.31e-02) involving several genes (1.95 to 4.30 fold change values), and the modulation of various genes involved in polyamine synthesis and in pro/counter-inflammatory signalling. CONCLUSIONS: Our findings suggest that the amastigote growth relies on early coordinated gene expression of the macrophage lipid and polyamine pathways. Moreover, these macrophages hosting multiplying L. amazonensis amastigotes display a transcriptional profile biased towards parasite-and host tissue-protective processes.
PMID: 19302708 [PubMed - as supplied by publisher]
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Related Articles
- Biogenesis of Leishmania-harbouring parasitophorous vacuoles following phagocytosis of the metacyclic promastigote or amastigote stages of the parasites. [J Cell Sci. 2002]
- H-2M molecules, like MHC class II molecules, are targeted to parasitophorous vacuoles of Leishmania-infected macrophages and internalized by amastigotes of L. amazonensis and L. mexicana. [J Cell Sci. 1999]
- ReviewUnveiling pathways used by Leishmania amazonensis amastigotes to subvert macrophage function. [Immunol Rev. 2007]
- Distribution of MHC class I and of MHC class II molecules in macrophages infected with Leishmania amazonensis. [J Cell Sci. 1994]
- ReviewAntiparasitic chemotherapy: tinkering with the purine salvage pathway. [Adv Exp Med Biol. 2008]
- 6: J Commun Dis. 2008 Jun;40(2):133-8.
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Dual culture method to determine the relationship of gut bacteria of sandfly (Phlebotomus argentipes) with promastigotes of Leishmania donovani.
Centre for Research in Medical Entomology, Indian Council of Medical Research, No. 4, Sarojini Street, China Chokkikulam, Madurai, 625002, India. mmuniaraj@yahoo.com
A simple dual culture agar plating technique has been developed and evaluated for its efficiency in determining the relationship of gut bacteria of sandfly with Leishmania donovani promastigotes. There are about twenty morphologically distinct bacterial colonies have been isolated from the gut homogenate of Phlebotomus argentipes. In dual culture method, each bacterial isolate was inoculated in one half of the plate and the promastigotes of Leishmania was inculcated in the other half by streaking. After incubation, the type of association was determined based on the presence or absence of promastigotes colonies. The reliability of this method was compared with broth dilution method in 96 well plate.
PMID: 19301698 [PubMed - in process]
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Related Articles
- Leishmania major and L. donovani: effects on proteolytic enzymes of Phlebotomus papatasi (Diptera, Psychodidae). [Exp Parasitol. 1986]
- The effect of anti-sandfly saliva antibodies on Phlebotomus argentipes and Leishmania donovani. [Int J Parasitol. 1998]
- High efficiency plating method for Leishmania promastigotes in semidefined or completely-defined medium. [J Parasitol. 1983]
- ReviewLeishmania differentiation in natural and unnatural sand fly hosts. [J Eukaryot Microbiol. 1993]
- ReviewNew insights into the developmental biology and transmission mechanisms of Leishmania. [Curr Mol Med. 2004]
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