Tuesday, May 26, 2009

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 -10 of 10

1: RNA. 2009 May 22. [Epub ahead of print]

Novel TUTase associates with an editosome-like complex in mitochondria of Trypanosoma brucei.

Aphasizheva I, Ringpis GE, Weng J, Gershon PD, Lathrop RH, Aphasizhev R.

Department of Microbiology and Molecular Genetics, School of Medicine, University of California at Irvine, Irvine, California 92697, USA.

Expression of mitochondrial genomes in Kinetoplastida protists requires massive uracil insertion/deletion mRNA editing. The cascade of editing reactions is accomplished by a multiprotein complex, the 20S editosome, and is directed by trans-acting guide RNAs. Two distinct RNA terminal uridylyl transferases (TUTases), RNA Editing TUTase 1 (RET1) and RNA Editing TUTase 2 (RET2), catalyze 3' uridylylation of guide RNAs and U-insertions into the mRNAs, respectively. RET1 is also involved in mitochondrial mRNA turnover and participates in numerous heterogeneous complexes; RET2 is an integral part of the 20S editosome, in which it forms a U-insertion subcomplex with zinc finger protein MP81 and RNA editing ligase REL2. Here we report the identification of a third mitochondrial TUTase from Trypanosoma brucei. The mitochondrial editosome-like complex associated TUTase (MEAT1) interacts with a 20S editosome-like particle, effectively substituting the U-insertion subcomplex. MEAT1 and RET2 are mutually exclusive in their respective complexes, which otherwise share several components. Similarly to RET2, MEAT1 is exclusively U-specific in vitro and is active on gapped double-stranded RNA resembling editing substrates. However, MEAT1 does not require a 5' phosphate group on the 3' mRNA cleavage fragment produced by editing endonucleases. The functional RNAi complementation experiments showed that MEAT1 is essential for viability of bloodstream and insect parasite forms. The growth inhibition phenotype in the latter can be rescued by coexpressing an RNAi-resistant gene with double-stranded RNA targeting the endogenous transcript. However, preliminary RNA analysis revealed no gross effects on RNA editing in MEAT1-depleted cells and indicated its possible role in regulating the mitochondrial RNA stability.

PMID: 19465686 [PubMed - as supplied by publisher]

2: RNA. 2009 May 22. [Epub ahead of print]

Mitochondrial tRNA import in Trypanosoma brucei is independent of thiolation and the Rieske protein.

Paris Z, Rubio MA, Lukes J, Alfonzo JD.

Biology Centre, Institute of Parasitology, Czech Academy of Sciences, 37005 Ceské Budejovice (Budweis), Czech Republic.

Due to a complete lack of the tRNA genes in the mitochondrial genome of Trypanosoma brucei, all tRNAs needed for mitochondrial translation have to be imported into the organelle from the cytosol. A previous study showed that the modified nucleotide s(2)U could act as a negative determinant for mitochondrial tRNA import in another kinetoplastid, Leishmania tarentolae. We have investigated whether the same type of cytosolic control for tRNA retention exists in T. brucei. Based on Northern analysis with subcellular RNA fractions and in vitro import assays, we demonstrate that silencing of the cysteine desulfurase, TbNfs (TbIscS), the key enzyme in tRNA thiolation (s(2)U) and Fe-S cluster formation in vivo, has no effect on tRNA partitioning. This observation is especially surprising in light of a recent report suggesting that in L. tropica the Rieske Fe-S protein is an essential component of the RNA import complex (RIC). In line with the above observation, we also show that down-regulation of the Rieske protein by RNA interference, similar to the TbNfs knockdowns, has no effect on import. The data presented here supports the view that in T. brucei: (1) s(2)U is not a negative determinant for tRNA import; (2) the Rieske protein is not an essential component of the import machinery, and (3) since the Rieske protein is essential for respiration and maintenance of inner mitochondrial membrane potential, neither process plays a critical role in tRNA import. We therefore suggest that the T. brucei import machinery differs substantially from what has been described in Leishmania.

PMID: 19465685 [PubMed - as supplied by publisher]

3: Trans R Soc Trop Med Hyg. 2009 May 21. [Epub ahead of print]

Description of a dermatropic Leishmania close to L. killicki (Rioux, Lanotte & Pratlong 1986) in Algeria.

Harrat Z, Boubidi SC, Pratlong F, Benikhlef R, Selt B, Dedet JP, Ravel C, Belkaid M.

Service d'Eco-Epidémiologie Parasitaire, Centre National de Référence des Leishmania, Institut Pasteur d'Algérie, Annexe de Sidi Fredj, Route du petit Staoueli, Dely Ibrahim, 16000 Alger, Algeria.

Cutaneous leishmaniasis (CL) is endemic in Algeria where two forms have been previously described, the sporadic form caused by Leishmania infantum in the north and the cutaneous form caused by L. major in central and southern parts of the country. During 2005, a CL outbreak occurred in the province of Ghardaïa, located in the north of Sahara, where 2040 cases were recorded, of which several were from urban areas. Six strains isolated from patients with active lesions were identified by isoenzyme electrophoresis and by molecular typing using systematic sequencing of a large subunit of the RNA polymerase. Four of the strains belonged to a new zymodeme, MON-301, close to L. killicki MON-8. The two other isolates were identified as L. major zymodeme MON-25. The new dermatropic Leishmania close to L. killicki is reported for the first time in Algeria and coexists sympatrically with L. major MON-25 in the region of Ghardaïa where they occur in their usual vectors of Phlebotomus papatasi (L. major) and P. sergenti (L. tropica). This new parasite demonstrates the need for further investigations to elucidate the life cycle and transmission of the emergent disease and to evaluate its phylogenetic position in the taxonomy of Leishmania.

PMID: 19464720 [PubMed - as supplied by publisher]

4: Med Clin (Barc). 2009 May 21. [Epub ahead of print]

[Cutaneous leishmaniasis associated with visceral leishmaniasis in a patient infected with human immunodeficiency virus.]

[Article in Spanish]

Gómez Moyano E, Hiraldo Gamero A, Sanz Trelles A, Jiménez Oñate F.

Servicio de Dermatología, Complejo Hospitalario Carlos Haya, Málaga, España.

PMID: 19464711 [PubMed - as supplied by publisher]

5: Vaccine. 2009 Jun 2;27(27):3505-3512. Epub 2009 Apr 8.

Decrease of the incidence of human and canine visceral leishmaniasis after dog vaccination with Leishmune((R)) in Brazilian endemic areas.

Palatnik-de-Sousa CB, Silva-Antunes I, Morgado AD, Menz I, Palatnik M, Lavor C.

Department of General Microbiology, Institute of Microbiology "Prof. Paulo de Góes", Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil.

Leishmune((R)), the first prophylactic vaccine licensed against canine visceral leishmaniasis (CVL), has been used in Brazil since 2004, where seropositive dogs are sacrificed in order to control human visceral leishmaniasis (VL). We demonstrate here that vaccination with Leishmune((R)) does not interfere with the serological control campaign (110,000 dogs). Only 1.3% of positivity (76 among 5860) was detected among Leishmune((R)) uninfected vaccinees. We also analyzed the possible additive effect of Leishmune((R)) vaccination over dog culling, on the decrease of the incidence of CVL and VL in two Brazilian endemic areas, from 2004 to 2006. In Araçatuba, a 25% of decline was seen in CVL with a 61% decline in human cases, indicating the additive effect of Leishmune((R)) vaccination of 5.7% of the healthy dogs (1419 dogs), on regular dog culling. In Belo Horizonte (BH), rising curves of canine and human incidence were observed in the districts of Barreiro, Venda Nova and Noroeste, while the canine and human incidence of Centro Sul, Leste, Nordeste, Norte, Pampulha and Oeste, started to decrease or maintained a stabilized plateau after Leishmune((R)) vaccination. Among the districts showing a percent decrease of human incidence (-36.5%), Centro Sul and Pampulha showed the highest dog vaccination percents (63.27% and 27.27%, respectively) and the lowest dog incidence (-3.36% and 1.89%, respectively). They were followed by Oeste, that vaccinated 25.30% of the animals and experienced an increase of only 12.86% of dog incidence and by Leste and Nordeste, with lower proportions of vaccinees (11.72% and 10.76%, respectively) and probably because of that, slightly higher canine incidences (42.77% and 35.73%). The only exception was found in Norte district where the reduced human and canine incidence were not correlated to Leishmune((R)) vaccination. Much lower proportions of dogs were vaccinated in Venda Nova (4.35%), Noroeste (10.27%) and Barreiro (0.09%) districts, which according to that exhibited very increased canine incidences (24.48%, 21.85% and 328.57%, respectively), and pronounced increases in human incidence (14%, 4% and 17%, respectively). The decrease of canine (p=-0.008) and human incidences (p=-0.048) is directly correlated to the increase of the number of vaccinated dogs, confirming the additive control effect of Leishmune((R)) vaccination over dog culling, reducing the parasite reservoir, protecting dogs and, in this way, reducing the risk of transmission of VL to humans and becoming a new effective control tool.

PMID: 19464528 [PubMed - as supplied by publisher]

6: Mol Biochem Parasitol. 2009 May 20. [Epub ahead of print]

The role of ATP-Binding Cassette (ABC) proteins in protozoan parasites.

Sauvage V, Aubert D, Escotte-Binet S, Villena I.

Laboratoire de Parasitologie-Mycologie, EA 3800, IFR 53, UFR Médecine, Université de Reims Champagne-Ardenne, 51 rue Cognacq-Jay, 51095 Reims cedex, France.

The ATP-binding cassette (ABC) superfamily is one of the largest protein families with representatives in all kingdoms of life. Members of this superfamily are involved in a wide variety of transport processes with substrates ranging from small ions to relatively large polypeptides and polysaccharides, but also in cellular processes such as DNA repair, translation or regulation of gene expression. For many years, the role of ABC proteins was mainly investigated for their implication in drug resistance. However, recent studies focused rather on their physiological functions for the parasite. In this review, we present an overview of ABC proteins in major protozoan parasites including Leishmania, Trypanosoma, Plasmodium, Toxoplasma, Cryptosporidium and Entamoeba species. We will also discuss the role of characterized ABC transporters in the biology of the parasite and in drug resistance.

PMID: 19464325 [PubMed - as supplied by publisher]

7: Mol Biochem Parasitol. 2009 May 19. [Epub ahead of print]

Mitochondrial Carrier Family Inventory of Trypanosoma brucei brucei: Identification, Expression and Subcellular Localisation.

Colasante C, Diaz PP, Clayton C, Voncken F.

Department of Biological Sciences and Hull York Medical School (HYMS), University of Hull, HU6 7RX Hull, United Kingdom.

The mitochondrial carrier family (MCF) is a group of structurally conserved proteins that mediate the transport of a wide range of metabolic intermediates across the mitochondrial inner membrane. In this paper, an overview of the mitochondrial carrier proteins (MCPs) of the early-branching kinetoplastid parasite Trypanosoma brucei brucei is presented. Sequence analysis and phylogenetic reconstruction gave insight into the evolution and conservation of the 24 identified TbMCPs; for most of these, putative transport functions could be predicted. Comparison of the kinetoplastid MCP inventory to those previously reported for other eukaryotes revealed remarkable deviations: T. b. brucei lacks genes encoding some prototypical MCF members, such as the citrate carrier and uncoupling proteins. The in vivo expression of the identified TbMCPs in the two replicating life-cycle forms of T. b. brucei, the bloodstream-form and procyclic-form, was quantitatively assessed at the mRNA level by northern blot analysis. Immunolocalisation studies confirmed that majority of the 24 identified TbMCPs is found in the mitochondrion of procyclic-form T. b. brucei.

PMID: 19463859 [PubMed - as supplied by publisher]

8: Exp Parasitol. 2009 May 19. [Epub ahead of print]

Leishmaniamajor: Effect of Protein Kinase A and Phosphodiesterase activity on infectivity and proliferation of promastigotes.

Malki-Feldman L, Jaffe CL.

Kuvin Center for the Study of Infectious and Tropical Diseases, Department of Microbiology and Molecular Genetics, P.O. Box 12272, Hebrew University - Hadassah Medical School, Jerusalem, Israel.

Effect of modulators on Protein kinase A (PKA) activity, promastigote growth and their ability to infect peritoneal macrophages was monitored. PKA inhibitors reduced [Protein Kinase Inhibitor (PKI) - 56%; H89 - 54.5%] kemptide phosphorylation by Leishmania major promastigote lysates, while activators increased phosphorylation (8-CPT-cAMP - 88%; Sp-cAMPS-AM - 152%). Activation was specifically inhibited by PKI. Phosphodiesterase inhibitors also increased kemptide phosphorylation (dipyridamole - 171%; rolipram - 106%; and 3-isobutyl-1-methyl-xanthine - 154%). Parasite proliferation was significantly retarded (200 nM H89; 100 muM myristoylate-PKI) or completely inhibited (500 nM H89) by culturing with PKA inhibitors. Incubation with dipyridamole or Sp-cAMPS-AM also inhibited proliferation. Brief treatment (2 hrs) with either H89, myristoylate-PKI, dipyridamole or Sp-cAMPS-AM reduced initial macrophage infection at days 1 and 2 (>40%) and on day 3 (>78% only for 100 mM myr-PKI). Characterization of leishmanial cAMP mediated signal transduction pathways will serve as the basis for the new drug design.

PMID: 19463817 [PubMed - as supplied by publisher]

Patient Drug Information

9: BMC Genomics. 2009 May 22;10(1):240. [Epub ahead of print]

Organization and evolution of two SIDER retroposon subfamilies and their impact on the Leishmania genome.

Smith M, Bringaud F, Papadopoulou B.

ABSTRACT: BACKGROUND: We have recently identified two large families of extinct transposable elements termed Short Interspersed DEgenerated Retroposons (SIDERs) in the parasitic protozoan Leishmania major. The characterization of SIDER elements was limited to the SIDER2 subfamily, although members of both subfamilies have been shown to play a role in the regulation of gene expression at the post-transcriptional level. Apparent functional domestication of SIDERs prompted further investigation of their characterization, dissemination and evolution throughout the Leishmania genus, with particular attention to the disregarded SIDER1 subfamily. RESULTS: Using optimized statistical profiles of both SIDER1 and SIDER2 subgroups, we report the first automated and highly sensitive annotation of SIDERs in the genomes of L. infantum, L. braziliensis and L. major. SIDER annotations were combined to in-silico mRNA extremity predictions to generate a detailed distribution map of the repeat family, hence uncovering an enrichment of antisense-oriented SIDER repeats between the polyadenylation and trans-splicing sites of intergenic regions, in contrast to the exclusive sense orientation of SIDER elements within 3'UTRs. Our data indicate that SIDER elements are quite uniformly dispersed throughout all three genomes and that their distribution is generally syntenic. However, only 47.4% of orthologous genes harbor a SIDER element in all three species. There is evidence for species-specific enrichment of SIDERs and for their preferential association, especially for SIDER2s, with different metabolic functions. Investigation of the sequence attributes and evolutionary relationship of SIDERs to other trypanosomatid retroposons reveals that SIDER1 is a truncated version of extinct autonomous ingi-like retroposons (DIREs), which were functional in the ancestral Leishmania genome. CONCLUSION: A detailed characterization of the sequence traits for both SIDER subfamilies unveils major differences. The SIDER1 subfamily is more heterogeneous and shows an evolutionary link with vestigial DIRE retroposons as previously observed for the ingi/RIME and L1Tc/NARTc couples identified in the T. brucei and T. cruzi genomes, whereas no identified DIREs are related to SIDER2 sequences. Although SIDER1s and SIDER2s display equivalent genomic distribution globally, the varying degrees of sequence conservation, preferential genomic disposition, and differential association to orthologous genes allude to an intricate web of SIDER assimilation in these parasitic organisms.

PMID: 19463167 [PubMed - as supplied by publisher]

10: Biomedica. 2008 Dec;28(4):597-606.

[PCR-RFLP and RAPD for typing neotropical Leishmania]

[Article in Spanish]

Montalvo AM, Monzote L, Fraga J, Montano I, Muskus C, Marín M, de Doncker S, Vélez ID, Dujardin JC.

Departamento de Parasitología, Instituto Pedro Kourí, La Habana, Cuba. amontalvo@ipk.sld.cu

INTRODUCTION: The analysis of the PCR-restriction fragment length polymorphism and random amplified polymorphic DNA have been useful tools for Leishmania identification. OBJECTIVES: Molecular procedures were demonstrated for identification and typing of reference strains of New World Leishmania and their applicability was validated for clinical samples. MATERIALS AND METHODS: DNA was extracted from 16 reference strains of Latin American Leishmania as well as from clinical samples of leishmaniasis patients. A sequence coding for cysteine proteinase B was amplified by PCR and subjected to restriction fragment length polymorphism analysis. The enzyme used was Taq1. For eight of the reference strains, the random amplified polymorphic desoxyribonucleic acid technique (RAPD) was applied. Band patterns for Leishmania species differentiation were established each each method. The sample size of the clinical sample was of 5. RESULTS: PCR products of the cysteine proteinase B gene were obtained for L. braziliensis, L. peruviana, L. panamensis and L. guyanensis. For the other species, L. mexicana, L. amazonensis, L. garnhami, L. lainsoni, L. chagasi, L. naiffi, no amplification occurred. The patterns of restriction fragments revealed band patterns in common for L. peruviana, L. guyanensis and L. panamensis, whereas L. braziliensis had a distinctive pattern. When human samples were examined, amplification occurred for all cases, and the profiles corresponded to the common profile of L. peruviana, L. guyanensis and L. panamensis. The RAPD technique demonstrated reproducible and distinctive patterns for each of the 8 reference strains, L. mexicana, L. amazonensis, L. garnhami, L. lainsoni, L. chagasi, L. naiffi, making possible to differentiate all them. The advantages and limitations of each procedure are discussed. CONCLUSIONS: The combination of RFP and RAPD methodologies provide useful tools to identify medical important species of Leishmania by recognizing DNA sequences characteristic of each species.

PMID: 19462565 [PubMed - in process]

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