Wednesday, May 20, 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 -7 of 7

1: Parasitol Res. 2009 May 12. [Epub ahead of print]Click here to read

Rapid detection of Leishmania infantum infection in dogs: a comparative study using fast agglutination screening test (FAST) and direct agglutination test (DAT) in Iran.

Babakhan L, Mohebali M, Akhoundi B, Edrissian GH, Keshavarz H.

Medical Parasitology and Mycology Department, Tehran University of Medical Sciences, Tehran, Iran.

Canine visceral leishmaniasis (CVL) is not only a veterinary problem but has also a serious public health importance. Rapid detection of CVL is highly important for control of human visceral leishmaniasis in Iran. This study was aimed to compare the fast agglutination screening test (FAST) with direct agglutination test (DAT) as a standard serological test for the detection of anti-Leishmania antibodies on dog serum samples. DAT and FAST antigens were prepared in the School of Public Health, Tehran University of Medical Science. Altogether, 73 serum samples from Leishmania infantum infection dogs and 74 sera from healthy controls were collected from human VL/CVL endemic and non-endemic areas of Iran, respectively. All the sera were evaluated with both FAST and DAT techniques. A sensitivity of 98.60% (95% CI, 98.57-98.62) and specificity of 78.70% (95 CI%, 69.20-88.20) were found at a 1:160 -(cut-off) titer when DAT confirmed cases were compared with healthy control. A good degree of agreement was observed between FAST and DAT (86.8%) by kappa analysis (p < 0.01). In conclusion, this study showed that FAST is very practical and simple diagnostic tool for the sero-diagnosis of CVL in endemic areas of Iran.

PMID: 19452168 [PubMed - as supplied by publisher]

2: Antimicrob Agents Chemother. 2009 May 18. [Epub ahead of print]Click here to read

Trypanocidal Activity of Genzyme 644131, an Adenosylmethionine Decarboxylase Inhibitor.

Bacchi CJ, Barker RH Jr, Rodriguez A, Hirth B, Rattendi D, Yarlett N, Hendrick CL, Sybertz E.

Haskins Laboratory, and Department of Biological and Health Sciences, Pace University, New York, New York 10038; Genzyme Corporation, Waltham, Massachusetts 02451; Department of Chemistry and Physical Sciences, Pace University, New York, New York 10038.

Genzyme 644131, 8-methyl-5'-{[(Z)-4-aminobut-2-enyl](methylamino)}adenosine, is an analog of the enzyme activated S-adenosylmethionine decarboxylase (AdoMetDC) inhibitor and trypanocidal agent MDL-7381, 5-{[(Z)-4-aminobut-2-enyl](methylamino)}adenosine. The analog differs from the parent in having an 8-methyl group on the purine ring which bestows favorable pharmacokinetic, biochemical and trypanocidal activities. The compound was curative in acute Trypanosoma brucei brucei and drug-resistant Trypanosoma brucei rhodesiense model infections, with single-dose activity in the 1-5 mg/kg/day QD dose range for 4 days against T. b. brucei, and 25-50 mg/kg BID dosing against T. b. rhodesiense infections. The compound was not curative in the TREU 667 CNS model infection, but cleared blood parasitemia and extended time to recrudescence in several groups. The study shows that AdoMetDC remains an attractive chemotherapeutic target in African trypanosomes and chemical changes in AdoMetDC inhibitors can produce more favorable drug characteristics than the lead compound.

PMID: 19451291 [PubMed - as supplied by publisher]

3: Mol Biochem Parasitol. 2009 Aug;166(2):186-9. Epub 2009 Mar 21.Click here to read

DRBD1 is the Trypanosoma brucei homologue of the Spliceosome-Associated Protein 49.

Manful T, Cristodero M, Clayton C.

Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), ZMBH-DKFZ Alliance, Im Neuenheimer Feld 282, D69120 Heidelberg, Germany.

The 5'-ends of all Kinetoplastid mRNAs consist of a short sequence added by trans splicing. In contrast to cis splicing in mammals, trans splicing in trypanosomes does not involve sequence-specific recognition of the branch point by the U2 snRNP. In mammalian cells and yeast, U2 snRNP is associated with the multimeric factor SF3b, which contains p14, SF3b10, SF3b14b, SAP49, SAP130, SAP145 and SAP155. The interaction between Trypanosoma cruzi p14 and SAP155 has already been characterised using the yeast 2-hybrid system. We here identify the Trypanosoma brucei RRM-protein DRBD1 as a homologue of SAP49. TAP-tagged DRBD1 co-purified with homologues of p14, SAP130, SAP145 and SAP155. Tagged DRBD1 was found in the nucleus; RNAi targeting DRBD1 inhibited trypanosome growth and caused a very mild splicing defect.

PMID: 19450735 [PubMed - in process]

4: Mol Biochem Parasitol. 2009 Aug;166(2):183-5. Epub 2009 Mar 13.Click here to read

Casein kinase 1 isoform 2 is essential for bloodstream form Trypanosoma brucei.

Urbaniak MD.

Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.

Induction of RNA interference targeted against casein kinase 1 isoform 2 (TbCK1.2, Tb927.5.800) in bloodstream form Trypanosoma brucei in vitro results in rapid cessation of growth, gross morphological changes, multinucleation and ultimately cell death. A null mutant of the highly homologous casein kinase 1 isoform 1 (Tb927.5.790) in bloodstream form T. brucei displays no growth or morphological phenotype in vitro. A truncated form of TbCK1.2 expressed in Escherichia coli as a GST fusion produces catalytically active recombinant protein, facilitating screening for small molecule inhibitors. These data show that TbCK1.2 is an attractive target for anti-trypanosomal drug discovery.

PMID: 19450734 [PubMed - in process]

5: Mol Biochem Parasitol. 2009 Aug;166(2):142-52. Epub 2009 Apr 5.Click here to read

The enzymes of the 10-formyl-tetrahydrofolate synthetic pathway are found exclusively in the cytosol of the trypanosomatid parasite Leishmania major.

Vickers TJ, Murta SM, Mandell MA, Beverley SM.

Department of Molecular Microbiology, Campus Box 8230, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA.

In most organisms 10-formyl-tetrahydrofolate (10-CHO-THF) participates in the synthesis of purines in the cytosol and formylation of mitochondrial initiator methionyl-tRNA(Met). Here we studied 10-CHO-THF biosynthesis in the protozoan parasite Leishmania major, a purine auxotroph. Two distinct synthetic enzymes are known, a bifunctional methylene-tetrahydrofolate dehydrogenase/cyclohydrolase (DHCH) or formyl-tetrahydrofolate ligase (FTL), and phylogenomic profiling revealed considerable diversity for these in trypanosomatids. All species surveyed contain a DHCH1, which was shown recently to be essential in L. major. A second DHCH2 occurred only in L. infantum, L. mexicana and T. cruzi, and as a pseudogene in L. major. DHCH2s bear N-terminal extensions and we showed a LiDHCH2-GFP fusion was targeted to the mitochondrion. FTLs were found in all species except Trypanosoma brucei. L. major ftl(-) null mutants were phenotypically normal in growth, differentiation, animal infectivity and sensitivity to a panel of pteridine analogs, but grew more slowly when starved for serine or glycine, as expected for amino acids that are substrates in C1-folate metabolism. Cell fractionation and western blotting showed that both L. major DHCH1 and FTL were localized to the cytosol and not the mitochondrion. These localization data predict that in L. major cytosolic 10-formyl-tetrahydrofolate must be transported into the mitochondrion to support methionyl-tRNA(Met) formylation. The retention in all the trypanosomatids of at least one enzyme involved in 10-formyl-tetrahydrofolate biosynthesis, and the essentiality of this metabolite in L. major, suggests that this pathway represents a promising new area for chemotherapeutic attack in these parasites.

PMID: 19450731 [PubMed - in process]

6: Dermatol Online J. 2009 Apr 15;15(4):9.

Diffuse Cutaneous Leishmaniasis in HIV.

Mehta V, Dil SK, Indusri L.

Dept of Skin and STD, Kasturba Hospital, Manipal, Karnataka, India. vandanamht@yahoo.com.

Cutaneous leishmaniasis is caused by the intracellular protozoan parasite belonging to the genus leishmania and is characterized by a myriad of clinical lesions including papules, nodules, and ulcers. Diffuse cutaneous forms of leishmaniasis are rare. We report a rare case from South India of diffuse cutaneous leishmaniasis masquerading as lepromatous leprosy in the context of HIV infection.

PMID: 19450402 [PubMed - in process]

7: BMC Genomics. 2009 May 18;10(1):232. [Epub ahead of print]Click here to read

Gene organization and sequence analyses of transfer RNA genes in Trypanosomatid parasites.

Padilla-Mejia NE, Florencio-Martinez LE, Figueroa-Angulo EE, Manning-Cela RG, Hernandez-Rivas R, Myler PJ, Martinez-Calvillo S.

ABSTRACT: BACKGROUND: The protozoan pathogens Leishmania major, Trypanosoma brucei and Trypanosoma cruzi (the Tritryps) are parasites that produce devastating human diseases. These organisms show very unusual mechanisms of gene expression, such as polycistronic transcription. We are interested in the study of tRNA genes, which are transcribed by RNA polymerase III (Pol III). To analyze the sequences and genomic organization of tRNA genes and other Pol III-transcribed genes, we have performed an in silico analysis of the Tritryps genome sequences. RESULTS: Our analysis indicated the presence of 83, 66 and 120 genes in L. major, T. brucei and T. cruzi, respectively. These numbers include several previously unannotated selenocysteine (Sec) tRNA genes. Most tRNA genes are organized into clusters of 2 to 10 genes that may contain other Pol III-transcribed genes. The distribution of genes in the L. major genome does not seem to be totally random, like in most organisms. While the majority of the tRNA clusters do not show synteny (conservation of gene order) between the Tritryps, a cluster of 13 Pol III genes that is highly syntenic was identified. We have determined consensus sequences for the putative promoter regions (Boxes A and B) of the Tritryp tRNA genes, and specific changes were found in tRNA-Sec genes. Analysis of transcription termination signals of the tRNAs (clusters of Ts) showed differences between T. cruzi and the other two species. We have also identified several tRNA isodecoder genes (having the same anticodon, but different sequences elsewhere in the tRNA body) in the Tritryps. CONCLUSION: A low number of tRNA genes is present in Tritryps. The overall weak synteny that they show indicates a reduced importance of genome location of Pol III genes compared to protein-coding genes. The fact that some of the differences between isodecoder genes occur in the internal promoter elements suggests that differential control of the expression of some isoacceptor tRNA genes in Tritryps is possible. The special characteristics found in Boxes A and B from tRNA-Sec genes from Tritryps indicate that the mechanisms that regulate their transcription might be different from those of other tRNA genes.

PMID: 19450263 [PubMed - as supplied by publisher]

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