What's new for 'Trypanosomatids' in PubMed

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Sent on Friday, 2010 Aug 13
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 - 3 of 3

1.	J Biol Chem. 2010 Aug 11. [Epub ahead of print] Ablation of succinate production from glucose metabolism in the procyclic trypanosomes induces metabolic switches to the Gly3p/DHAP shuttle and to proline metabolism. Ebikeme C, Hubert J, Biran M, Gouspillou G, Morand P, Plazolles N, Guegan F, Diolez P, Franconi JM, Portais JC, Bringaud F. UMR5536 CNRS, France; Abstract Trypanosoma brucei is a parasitic protist that undergoes a complex life cycle during transmission from its mammalian host (bloodstream forms) to the midgut of its insect vector (procyclic form). In both parasitic forms, most glycolytic steps take place within specialized peroxisomes, called glycosomes. Here we studied metabolic adaptations in procyclic trypanosome mutants affected in their maintenance of the glycosomal redox balance. T. brucei can theoretically use three strategies to maintain the glycosomal NAD+/NADH balance, (i) the glycosomal succinic fermentation branch, (ii) the glycerol-3-phosphate (Gly3P) / dihydroxyacetone-phosphate (DHAP) shuttle that transfers reducing equivalents to the mitochondrion and (iii) the glycosomal glycerol production pathway. We showed a hierarchy in the use of these glycosomal NADH-consuming pathways by determining metabolic perturbations and adaptations in single and double mutant cell lines using a combination of NMR, IC-MS/MS and HPLC approaches. Although functional, the Gly3P/DHAP shuttle is primarily used when the preferred succinate fermentation pathway is abolished in the pepck mutant cell line. In the absence of these two pathways (Deltapepck/RNAiFAD-GPDH.i mutant), glycerol production is used, but with a 16-fold reduced glycolytic flux. In addition, the pepck mutant cell line shows a 3.3-fold reduced glycolytic flux compensated by an increase of proline metabolism. The inability of the Deltapepck mutant to maintain a high glycolytic flux demonstrates that the Gly3P/DHAP shuttle is not adapted to the procyclic trypanosome context. In contrast, this shuttle was shown earlier to be the only way used by the bloodstream forms of T. brucei to sustain their high glycolytic flux.
	PMID: 20702405 [PubMed - as supplied by publisher]
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2.	Mem Inst Oswaldo Cruz. 2010 May;105(3):239-45. The biological in vitro effect and selectivity of aromatic dicationic compounds on Trypanosoma cruzi. da Silva CF, da Silva PB, Batista MM, Daliry A, Tidwell RR, Soeiro Mde N. Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ, Brasil. Abstract Trypanosoma cruzi is a parasite that causes Chagas disease, which affects millions of individuals in endemic areas of Latin America. One hundred years after the discovery of Chagas disease, it is still considered a neglected illness because the available drugs are unsatisfactory. Aromatic compounds represent an important class of DNA minor groove-binding ligands that exhibit potent antimicrobial activity. This study focused on the in vitro activity of 10 aromatic dicationic compounds against bloodstream trypomastigotes and intracellular forms of T. cruzi. Our data demonstrated that these compounds display trypanocidal effects against both forms of the parasite and that seven out of the 10 compounds presented higher anti-parasitic activity against intracellular parasites compared with the bloodstream forms. Additional assays to determine the potential toxicity to mammalian cells showed that the majority of the dicationic compounds did not considerably decrease cellular viability. Fluorescent microscopy analysis demonstrated that although all compounds were localised to a greater extent within the kinetoplast than the nucleus, no correlation could be found between compound activity and kDNA accumulation. The present results stimulate further investigations of this class of compounds for the rational design of new chemotherapeutic agents for Chagas disease. Free Article
	PMID: 20512235 [PubMed - indexed for MEDLINE]
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3.	Microbes Infect. 2010 Jul;12(7):511-7. Epub 2010 Mar 27. The innate immune response to Trypanosoma cruzi infe ction. Kayama H, Takeda K. Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan. Abstract Trypanosoma cruzi infection is a major public health problem in Latin America. The host innate immune system plays a pivotal role in the recognition of T. cruzi infection and the subsequent development of adaptive immunity. In this review, we focus on the TLR-dependent and -independent innate immune responses to T. cruzi.
	PMID: 20348008 [PubMed - indexed for MEDLINE]
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