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Sent on Saturday, 2011 Jun 04Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | PLoS One. 2011;6(5):e19851. Epub 2011 May 27.Visualisation of Leishmania donovani Fluorescent Hybrids during Early Stage Development in the Sand Fly Vector.Sadlova J, Yeo M, Seblova V, Lewis MD, Mauricio I, Volf P, Miles MA.SourceDepartment of Parasitology, Faculty of Science, Charles University, Prague, Czech Republic. AbstractBACKGROUND:The Leishmania protozoan parasites cause devastating human diseases. Leishmania have been considered to replicate clonally, without genetic exchange. However, an accumulation of evidence indicates that there are inter-specific and intra-specific hybrids among natural populations. The first and so far only experimental proof of genetic exchange was obtained in 2009 when double drug resistant Leishmania major hybrids were produced by co-infecting sand flies with two strains carrying different drug resistance markers. However, the location and timing of hybridisation events in sand flies has not been described. METHODOLOGY/PRINCIPAL FINDINGS:Here we have co-infected Phlebotomus perniciosus and Lutzomyia longipalpis with transgenic promastigotes of Leishmania donovani strains carrying hygromycin or neomycin resistance genes and red or green fluorescent markers. Fed females were dissected at different times post bloodmeal (PBM) and examined by fluorescent microscopy or fluorescent activated cell sorting (FACS) followed by confocal microscopy. In mixed infections strains LEM3804 and Gebre-1 reached the cardia and stomodeal valves more rapidly than strains LEM4265 and LV9. Hybrids unequivocally expressing both red and green fluorescence were seen in single flies of both vectors tested, co-infected with LEM4265 and Gebre-1. The hybrids were present as short (procyclic) promastigotes 2 days PBM in the semi-digested blood in the endoperitrophic space. Recovery of a clearly co-expressing hybrid was also achieved by FACS. However, hybrids could not sustain growth in vitro. CONCLUSIONS/SIGNIFICANCE:For the first time, we observed L. donovani hybrids in the sand fly vector, 2 days PBM and described the morphological stages involved. Fluorescence microscopy in combination with FACS allows visualisation and recovery of the progeny of experimental crosses but on this occasion the hybrids were not viable in vitro. Nevertheless, genetic exchange in L. donovani has profound epidemiological significance, because it facilitates the emergence and spread of new phenotypic traits. |
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| 2. | J Signal Transduct. 2011;2011:971968. Epub 2011 Feb 27.Parasite mitogen-activated protein kinases as drug discovery targets to treat human protozoan pathogens.Brumlik MJ, Pandeswara S, Ludwig SM, Murthy K, Curiel TJ.SourceDepartment of Medicine, School of Medicine, and Program in Immunology and Microbiology, Graduate School of Biomedical Sciences, University of Texas Health Science Center, San Antonio, TX 78229, USA. AbstractProtozoan pathogens are a highly diverse group of unicellular organisms, several of which are significant human pathogens. One group of protozoan pathogens includes obligate intracellular parasites such as agents of malaria, leishmaniasis, babesiosis, and toxoplasmosis. The other group includes extracellular pathogens such as agents of giardiasis and amebiasis. An unfortunate unifying theme for most human protozoan pathogens is that highly effective treatments for them are generally lacking. We will review targeting protozoan mitogen-activated protein kinases (MAPKs) as a novel drug discovery approach towards developing better therapies, focusing on Plasmodia, Leishmania, and Toxoplasma, about which the most is known. |
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| 3. | Enzyme Res. 2011;2011:230542. Epub 2011 May 2.Identification of a Functional Type IA Topoisomerase, LdTopIIIβ, from Kinetoplastid Parasite Leishmania donovani.Banerjee B, Sen N, Majumder HK.SourceMolecular Parasitology Laboratory, Infectious Disease and Immunology Division, Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Kolkata 700032, India. AbstractDNA topoisomerases of kinetoplastids represent a family of DNA processing enzymes that essentially solve the topological problems not only in nuclear DNA but also in kinetoplast DNA. We have, for the first time, identified a Leishmania donovani homologue of bacterial and eukaryotic IA type of topoisomerase III protein and termed as LdTopIIIβ. Complementation study of wild-type and mutant LdTopIIIβ with slow-growing topoisomerase III mutant yeast S. cerevisiae revealed the functional conservation of the leishmanial counterpart of topoisomerase IIIβ protein, the 327 tyrosine being the active site amino acid. A C-terminal deletion construct of LdTopIIIβ could not suppress the slow-growth phenotype of mutant yeast, indicating the requirement of C-terminal region for the enzyme function in vivo.LdTopIIIβ localized inside the nucleus and kinetoplast of the parasite. Taken together, our study indicates functional conservation and possible role of LdTopIIIβ in parasite DNA processing. |
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| 4. | J Biol Chem. 2011 Jun 2. [Epub ahead of print]Isoptopomer profiling of Leishmania mexicana promastigotes reveals important roles for succinate fermentation and aspartate uptake in TCA cycle anaplerosis, glutamate synthesis and growth.Saunders EC, Ng WW, Chamber JM, Ng M, Naderer T, Kroemer JO, Likic VA, McConville MJ.SourceUniversity of Melbourne, Australia; AbstractLeishmania parasites proliferate within nutritionally complex niches in their sandfly vector and mammalian hosts. However, the extent to which these parasites utilize different carbon sources remains poorly defined. In this study we have followed the incorporation of various (13)C-labeled carbon sources into the intracellular and secreted metabolites of L. mexicana promastigotes using gas chromatography-mass spectrometry and (13)C-NMR. (13)C-U-glucose was rapidly incorporated into intermediates in glycolysis, the pentose phosphate pathway and the cytoplasmic carbohydrate reserve material, mannogen. Enzymes involved in the upper glycolytic pathway are sequestered within glycosomes, and the ATP and NAD(+) consumed by these reactions were primarily regenerated by the fermentation of phosphoenolpyruvate to succinate (glycosomal succinate fermentaion). The initiating enzyme in this pathway, PEP carboxykinase, was exclusively localized to the glycosome. While some of the glycosomal succinate was secreted, most of the C4 dicarboxylic acids generated during succinate fermentation were further catabolized in the TCA cycle. A high rate of TCA cycle anaplerosis was further suggested by measurement of (13)C-aspartate and (13)C-alanine uptake and catabolism. TCA cycle anaplerosis is apparently needed to sustain glutamate production under standard culture conditions. Specifically, inhibition of mitochondrial aconitase with sodium fluoroacetate resulted in the rapid depletion of intracellular glutamate pools and growth arrest. Addition of high concentrations of exogenous glutamate alleviated this growth arrest. These findings suggest that glycosomal and mitochondrial metabolism in Leishmania promastigotes is tightly coupled and that, in contrast to the situation in some other trypanosomatid parasites, the TCA cycle has crucial anabolic functions. |
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| 5. | J Vector Ecol. 2011 Jun;36(1):153-8. doi: 10.1111/j.1948-7134.2011.00152.x.Morphometric and morphological variation between two different populations of Phlebotomus major s.l. from endemic and non-endemic foci of visceral leishmaniasis in Iran.Badakhshan M, Sadraei J, Moin-Vaziri V.SourceDepartment of Medical Parasitology and Entomology, College of Medical Sciences, Tarbiat Modares University, Tehran, Iran Department of Parasitology and Mycology, School of Medicine, Shahid Beheshti University of Medical Sciences. Tehran, Iran. AbstractPopulations of Phlebotomus major were examined in two endemic and nonendemic foci of visceral leishmaniasis in Iran. Based on the shape of the aedeagus and ventrally located hairs of coxite and pharyngeal armatures, two morphotypes were found sympatrically in the endemic area of Borazjan. Significant differences in morphometric survey were observed in at least 11 measured characters. The aedeagus of the non-endemic Miyandoab morphotype, and also of a few specimens from Borazjan, is completely parallel throughout its length with a slightly expanded end. Ventrally located hairs of the middle coxite were longer and more compact. It is close morphologically to P. major neglectus (P. neglectus), which was recently recorded from Iran. It is also morphologically similar to P. notus, which has not yet been reported from Iran and needs further investigation. The aedeagus of the morphotype occurring only in Borazjan is narrower in the middle and the hairs are closer to the base of the coxite and are shorter and more outspread, which makes it similar to P. major krimensis or P. neglectus. The two morphotypes occurring sympatrically in Borazjan do not appear to be subspecies and it may be premature to propose them as separate species. Further investigation is needed to clarify the actual status of P. major s. l. in Iran. © 2011 The Society for Vector Ecology. |
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| 6. | Chem Biol Drug Des. 2011 Mar;77(3):166-72. doi: 10.1111/j.1747-0285.2010.01071.x. Epub 2011 Jan 19.Synthesis of 2-hydrazolyl-4-thiazolidinones based on multicomponent reactions and biological evaluation against Trypanosoma Cruzi.Pizzo C, Saiz C, Talevi A, Gavernet L, Palestro P, Bellera C, Blanch LB, Benítez D, Cazzulo JJ, Chidichimo A, Wipf P, Mahler SG.SourceDepartamento de Química Orgánica, Cátedra de Química Farmacéutica, Universidad de la República (UdelaR), Avda. General Flores 2124, CC1157 Montevideo, Uruguay. AbstractA series of 18 novel 2-hydrazolyl-4-thiazolidinones-5-carboxylic acids, amides and 5,6-α,β-unsaturated esters were synthesized, and their in vitro activity on cruzipain and T. cruzi epimastigotes was determined. Some agents show activity at 37 μm concentration in the enzyme assay. Computational tools and docking were used to correlate the biological response with the physicochemical parameters of the compounds and their cruzipain inhibitory effects. © 2011 John Wiley & Sons A/S. |
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