Friday, September 18, 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 -6 of 6

1: PLoS One. 2009 Sep 17;4(9):e7074.

PSSA-2, a Membrane-Spanning Phosphoprotein of Trypanosoma brucei, Is Required for Efficient Maturation of Infection.

Fragoso CM, Schumann Burkard G, Oberle M, Renggli CK, Hilzinger K, Roditi I.

Institut für Zellbiologie, Universität Bern, Bern, Switzerland.

The coat of Trypanosoma brucei consists mainly of glycosylphosphatidylinositol-anchored proteins that are present in several million copies and are characteristic of defined stages of the life cycle. While these major components of the coats of bloodstream forms and procyclic (insect midgut) forms are well characterised, very little is known about less abundant stage-regulated surface proteins and their roles in infection and transmission. By creating epitope-tagged versions of procyclic-specific surface antigen 2 (PSSA-2) we demonstrated that it is a membrane-spanning protein that is expressed by several different life cycle stages in tsetse flies, but not by parasites in the mammalian bloodstream. In common with other membrane-spanning proteins in T. brucei, PSSA-2 requires its cytoplasmic domain in order to exit the endoplasmic reticulum. Correct localisation of PSSA-2 requires phosphorylation of a cytoplasmic threonine residue (T(305)), a modification that depends on the presence of TbMAPK4. Mutation of T(305) to alanine (T(305)A) has no effect on the localisation of the protein in cells that express wild type PSSA-2. In contrast, this protein is largely intracellular when expressed in a null mutant background. A variant with a T(305)D mutation gives strong surface expression in both the wild type and null mutant, but slows growth of the cells, suggesting that it may function as a dominant negative mutant. The PSSA-2 null mutant exhibits no perceptible phenotype in culture and is fully competent at establishing midgut infections in tsetse, but is defective in colonising the salivary glands and the production of infectious metacyclic forms. Given the protein's structure and the effects of mutation of T(305) on proliferation and localisation, we postulate that PSSA-2 might sense and transmit signals that contribute to the parasite's decision to divide, differentiate or migrate.

PMID: 19759911 [PubMed - in process]

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2: J Clin Microbiol. 2009 Sep 16. [Epub ahead of print]

ANTIGENEMIA IN PATIENTS WITH MEDITERRANEAN VISCERAL LEISHMANIASIS.

Ferrua B, Rol N, Michel G, Marty P.

Université de Nice Sophia Antipolis, Faculté de Médecine, Nice, F-06107 cedex 2, France; INSERM, U895, Centre Méditerranéen de Médecine Moléculaire (C3M), Equipe 6, toxines microbiennes dans la relation hôte-pathogène, Nice, F-06204 cedex 3, France; Centre Hospitalier Universitaire de Nice, Laboratoire de Parasitologie-Mycologie, Nice, F-06202 cedex 3, France.

Antigenemia was retrospectively assessed in patients with Mediterranean Visceral Leishmaniasis (MVL) due to Leishmania infantum, by sandwich ELISA. Circulating Leishmania antigens were evidenced, partially under free form, in 53% of serum from immunocompetent individuals with MVL. Following successful therapy antigenemia decline as measured by ELISA, was more pronounced than antibody decrease.

PMID: 19759231 [PubMed - as supplied by publisher]

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3: Mol Biol Cell. 2009 Sep 16. [Epub ahead of print]

Streamlined Architecture and GPI-dependent Trafficking in the Early Secretory Pathway of African Trypanosomes.

Sevova ES, Bangs JD.

Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706.

Monitoring Editor: Benjamin S. Glick The variant surface glycoprotein (VSG) of bloodstream form Trypanosoma brucei is a critical virulence factor. The VSG GPI-anchor strongly influences passage through the early secretory pathway. Using a dominant negative mutation of TbSar1 we show that ER exit of secretory cargo in trypanosomes is dependent on the COPII machinery. Trypanosomes have two orthologues each of the Sec23 and Sec24 COPII subunits, which form specific heterodimeric pairs: TbSec23.1/TbSec24.2 and TbSec23.2/TbSec24.1. RNAi silencing of each subunit is lethal, but has minimal effects on trafficking of soluble and transmembrane proteins. However, silencing of the TbSec23.2/TbSec24.1 pair selectively impairs ER exit of GPI-anchored cargo. All four subunits colocalize to one or two ER exit sites (ERES), in close alignment with the post-nuclear flagellar adherence zone (FAZ), and closely juxtaposed to corresponding Golgi clusters. These ERES are nucleated on the FAZ-associated ER. The Golgi matrix protein TbGRASP defines a region between the ERES and Golgi suggesting a possible structural role in the ERES:Golgi junction. Our results confirm a selective mechanism for GPI-anchored cargo loading into COPII vesicles, and a remarkable degree of streamlining in the early secretory pathway. This unusual architecture likely maximizes efficiency of VSG transport and fidelity in organellar segregation during cytokinesis.

PMID: 19759175 [PubMed - as supplied by publisher]

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4: Vet J. 2009 Sep 14. [Epub ahead of print]

Serum concentrations of the derivatives of reactive oxygen metabolites (d-ROMs) in dogs with leishmaniosis.

Paltrinieri S, Ravicini S, Rossi G, Roura X.

Department of Veterinary Pathology, Hygiene and Public Health, University of Milan, Italy.

Leishmania infantum interferes with the oxidative metabolism of phagocytes. In order to assess whether derivatives of reactive oxygen metabolites (d-ROMs) decrease due to infection or increase due to inflammation, d-ROMs were measured in serum collected from control dogs (Group 1; n=12), from dogs seropositive for Leishmania either symptomatic (Group 2; n=27) or not (Group 3; n=14), and from dogs with other diseases (Group 4; n=16). The concentrations of d-ROMs in the four groups, expressed in Carratelli Units (U CARR) were, respectively, 75.4+/-39.5 (median, 81.6), 108.2+/-96.3 (73.4), 73.5+/-62.2 (62.0), 127.7+/-97.3 (94.3). There were no significant differences between groups, but dogs with values higher than the reference interval were found, mostly in Groups 2 and 4 (which had serum C-reactive protein levels consistent with inflammation), whilst low values were occasionally found in Groups 2 and 3. Inflammation may mask decreases in d-ROMs induced by Leishmania infection.

PMID: 19758830 [PubMed - as supplied by publisher]

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5: Euro Surveill. 2009 Sep 10;14(36). pii: 19327.

Imported human African trypanosomiasis in Europe, 2005-2009.

Gautret P, Clerinx J, Caumes E, Simon F, Jensenius M, Loutan L, Schlagenhauf P, Castelli F, Freedman D, Miller A, Bronner U, Parola P.

Infectious and Tropical Disease Unit, Hopital Nord AP-HM, Marseille, France. surveillance@eurotravnet.eu

Physicians in Europe are likely to see more African trypanosomiasis cases because of the increasing popularity of travel to Africa. In this paper the literature on imported cases in Europe, since 2005 is reviewed. Because of the high mortality risk associated with acute Rhodesian trypanosomiasis, travellers should be informed about preventive measures and the early disease manifestations.

PMID: 19758542 [PubMed - in process]

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6: J Med Chem. 2009 Sep 24;52(18):5763-7.

Synthesis and antiprotozoal properties of pentamidine congeners bearing the benzofuran motif.

Bakunov SA, Bakunova SM, Bridges AS, Wenzler T, Barszcz T, Werbovetz KA, Brun R, Tidwell RR.

Department of Pathology and Laboratory Medicine, School of Medicine, The University of North Carolina, Chapel Hill, North Carolina 27599-7525.

Forty-eight cationically substituted pentamidine congeners possessing benzofuran rings were synthesized by a copper mediated heteroannulation of substituted o-iodophenols with phenyl acetylenes. Activities of compounds 1-48 against Trypanosoma brucei rhodesiense, Plasmodium falciparum, and Leishmania donovani and cytotoxicities for mammalian cells were influenced by the nature of cationic substituents, placement of the benzofuran fragment, and the length of the carbon linker between aromatic moieties. Several dications exhibited superior antiplasmodial and antileishmanial potencies compared to pentamidine.

PMID: 19757840 [PubMed - in process]

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