Friday, May 1, 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 -5 of 5

1: Mol Divers. 2009 Apr 29. [Epub ahead of print]Click here to read

Structural analysis of trypanosomal sirtuin: an insight for selective drug design.

Kaur S, Shivange AV, Roy N.

Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S Nagar, Mohali, Punjab, 160062, India.

The infectious disease burden imposed by trypanosomatidae family continues to create burden in countries that are least equipped to bring new medicines to the clinic. For sickness caused by this family of parasites (African trypanosomiasis, Chagas disease, and leishmaniasis) no vaccines are available, and currently available drugs suffer from insufficient efficacy, excessive toxicity, and steady loss of effectiveness due to resistance. Availability of the genome sequence of pathogens of this family offers a unique avenue for the identification of novel common drug targets for all three pathogens. Sirtuin family of nicotinamide adenine dinucleotide (NAD)-dependent deacetylases are remarkably conserved throughout evolution from archaebacteria to eukaryotes and plays an important role in trypanosomatidae biology and virulence. In order to gain insight for selective drug design, three-dimensional (3D) models of L. major, L. infantum, T. brucie, and T. cruzi sirtuin were constructed by homology modeling and compared with human sirtuin. The molecular electrostatic potentials and cavity depth analysis of these models suggest that the inhibitor binding catalytic domain has various minor structural differences in the active site of trypanosomal and human sirtuin, regardless of sequence similarity. These studies have implications for designing effective strategies to identify inhibitors that can be developed as novel broad-spectrum antitrypanosomal drugs.

PMID: 19404761 [PubMed - as supplied by publisher]

2: Clin Vaccine Immunol. 2009 Apr 29. [Epub ahead of print]Click here to read

9-O-acetylated sialoglycoproteins: Important immunomodulators in Indian visceral leishmaniasis.

Ghoshal A, Mukhopadhyay S, Saha B, Mandal C.

Infectious diseases and Immunology Division, Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata-700 032; Department of Laboratory Medicine and Serology and Department of Tropical Medicine, School of Tropical Medicine, Calcutta 700073, INDIA.

Over expression of disease-associated 9-O-acetylated sialoglycoproteins (9-O-AcSGPs) on peripheral blood mononuclear cells (PBMC) of VL patients (PBMCVL) has been demonstrated as compared to healthy individuals using a lectin, Achatinin-H, with specificity towards 9-O-AcSAalpha2-6GalNAc. The decreased presence of disease associated 9-O-AcSGPs on different immune cells of parasitologically cured post-treated individuals relative to the untreated active VL patients was demonstrated. However, their contributory role as immunomodulatory determinants on PBMCVL remained unexplored. Accordingly, 9-O-AcSGPs on PBMCVL was sensitized with Achatinin-H leading to their enhanced proliferation as compared to that observed with different known mitogens or parasite antigen. This lypmhoproliferative response was characterized by evaluation of TH1/TH2 response by intracellular staining and ELISA for secreted cytokines, which was corroborated by their genetic expression. Sensitized PBMCVL evidenced a mixed TH1/TH2 cellular response with a predominance of the TH1 response, indicating the ability of 9-O-AcSGPs in modulating the host cell towards a favorable response. Interestingly, humoral and cellular response showed a good correlation. Further high levels of anti-9-O-AcSGPs antibodies in the order of distribution IgM>IgG1=IgG3>IgG4>IgG2>IgE could be explained by the preponderance of a mixed TH1/TH2 response. A good correlation of enhanced 9-O-AcSGPs with both cell mediated (r=0.98) and humoral (r=0.99) response was observed. In summary, it may be concluded that sensitization of 9-O-AcSGPs on PBMCVL mayprovide a basis for the modulation of the host's immune response by their controlled expression leading towards a beneficial immune response influencing the disease pathology.

PMID: 19403782 [PubMed - as supplied by publisher]

3: Clin Vaccine Immunol. 2009 Apr 29. [Epub ahead of print]Click here to read

Towards a new reference test for surra in camels.

Tran T, Claes F, Verloo D, De Greve H, Büscher P.

Department of Parasitology, Institute of Tropical Medicine, Nationalestraat 155, 2000 Antwerp, Belgium; Department of Molecular and Cellular Interactions, VIB, Brussels, Belgium; Laboratory of Molecular and Cellular Immunology, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium; Department of Biosystems, Katholieke Universiteit Leuven, Kasteelpark Arenberg 30 - bus 2456, B-3001 Heverlee, Belgium; Department of Scientific Cooperation and Assistance, European Food Safety Authority, Largo N. Palli 5/A, I-43100 Parma, Italy.

Current serological diagnosis of Trypanosoma evansi infection in camels is based on the native variable antigen type RoTat 1.2. The goal of this study is to develop a novel serological diagnostic test based on a non-variable protein and freed from the use of rats or mice for its production. An enzyme-linked immunosorbent assay using recombinant extracellular domain of Invariant Surface Glycoprotein 75 (ELISA/ISG75) was developed and tested on a collection of 184 camel sera. The results were compared to those obtained from three established antibody detection tests based on variable surface glycoprotein RoTat 1.2, in casu ELISA/T. evansi, card agglutination test for trypanosomiasis (CATT/T. evansi) and immune trypanolysis assay (TL). ELISA/ISG75 and ELISA/T. evansi show a sensitivity of 94.6% (95% confidence interval, CI, 87.8 - 98.2, at 19 percent positivity (PP) cut-off value) and 98.9% (95% CI 94.1 - 99.8, at 12 PP cut-off value) respectively. ELISA/ISG75 has 100% specificity (CI 95.9 - 100), while ELISA/T. evansi shows 98.9% specificity (CI 95.9 - 100). ELISA/ISG75 demonstrates an almost perfect agreement with TL, CATT/T. evansi, and ELISA/T. evansi, with Kappa scores of at least 0.94. The ELISA/ISG75 having a comparable performance as the gold standard (TL) and being independent of antigenic variation may become a new reference test for surra in camels. It opens avenues for diagnosis of T. evansi infections in other hosts as well as the development of a pan-Trypanozoon test for detection of T. b. brucei, T. b. gambiense, T. b. rhodesiense, T. evansi and T. equiperdum.

PMID: 19403780 [PubMed - as supplied by publisher]

4: Emerg Infect Dis. 2009 May;15(5):795-8.

Canine leishmaniasis in southeastern Spain.

Martín-Sánchez J, Morales-Yuste M, Acedo-Sánchez C, Barón S, Díaz V, Morillas-Márquez F.

Universidad de Granada, Granada, Spain. joaquina@ugr.es

To examine prevalence changes and risk factors for canine leishmaniasis, we conducted a cross-sectional seroprevalence study and a survey during April-June 2006. Seroprevalence had increased at the meso-Mediterranean bioclimatic level over 22 years. Risk was highest for dogs that were older, large, lived outside, and lived at the meso-Mediterranean level.

PMID: 19402973 [PubMed - in process]

5: Infect Genet Evol. 2009 Jan;9(1):81-6. Epub 2008 Nov 5.Click here to read Nucleotide, LinkOut

Phylogenetic analysis reveals the presence of the Trypanosoma cruzi clade in African terrestrial mammals.

Hamilton PB, Adams ER, Njiokou F, Gibson WC, Cuny G, Herder S.

School of Biosciences, University of Exeter, Exeter, UK. p.b.hamilton@exeter.ac.uk

Despite the impact of some trypanosome species on human and livestock health, the full diversity of trypanosomes in Africa is poorly understood. A recent study examined the prevalence of trypanosomes among a wide variety of wild vertebrates in Cameroon using species-specific PCR tests, but six trypanosome isolates remained unidentified. Here they have been re-examined using fluorescent fragment length barcoding (FFLB) and phylogenetic analysis of glycosomal glyceraldehyde phosphate dehydrogenase gGAPDH and 18S ribosomal RNA (rDNA) genes. Isolates from a monkey (Cercopithecus nictitans) and a palm civet (Nandinia binotata) belonged to the Trypanosoma cruzi clade, known previously only from New World and Australian terrestrial mammals, and bats from Africa, Europe and South America. Of the four other isolates, three from antelope were identified as Trypanosoma theileri, and one from a crocodile as T. grayi. This is the first report of trypanosomes of the T. cruzi clade in African terrestrial mammals and expands the clade's known global distribution in terrestrial mammals. Previously it has been hypothesized that African and New World trypanosomes diverged after continental separation, dating the divergence to around 100 million years ago. The new evidence instead suggests that intercontinental transfer occurred well after this, possibly via bats or rodents, allowing these trypanosomes to establish and evolve in African terrestrial mammals, and questioning the validity of calibrating trypanosome molecular trees using continental separation.

PMID: 19027884 [PubMed - indexed for MEDLINE]

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