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Involvement of a Leishmania thymidine kinase in flagellum formation, promastigote shape and growth as well as virulence

Thiel, Meike and Harder, Simone and Wiese, Martin and Kroemer, Manfred and Bruchhaus, Iris (2008) Involvement of a Leishmania thymidine kinase in flagellum formation, promastigote shape and growth as well as virulence. Molecular and Biochemical Parasitology, 158 (2). pp. 152-162. ISSN 0166-6851

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Abstract

Leishmania promastigote cells transmitted by their insect vector get phagocytosed by macrophages and convert into the amastigote form. In a recently performed proteomic study, a thymidine kinase (TK) was found to be preferentially expressed in amastigotes. Western blot analysis showing a marked increase in TK protein synthesis during stage differentiation from promastigotes to amastigotes confirmed this result. After comparison of the amino acid sequence of Leishmania donovani and Leishmania major thymidine kinases with thymidine kinases of other organisms the Leishmania protein has to be classified as a type II TK. Therefore, in accordance with the nomenclature of other thymidine kinases we named the Leishmania enzymes LdTK1 and LmTK1, respectively. The LdTK1 is localised within the cytoplasm of promastigotes. In amastigotes, increased expression and a clustered distribution of the protein can be observed. Lmtk1 single allele gene replacement mutants have significantly elongated flagellum. In contrast, lmtk1 double allele gene replacement mutants show a remarkably reduced flagellar length, diminished overall size and a deformed body shape. In addition, they have a 12-fold reduced growth rate. For both mutant strains, macrophage infectivity is clearly reduced compared to a L. major wildtype infection.

Item type: Article
ID code: 13251
Keywords: leishmania donovani, leishmania major, thymidine kinase, stage differentiation, gene knockout, pharmacology, Therapeutics. Pharmacology, Pharmacy and materia medica, Microbiology, Molecular Biology, Parasitology
Subjects: Medicine > Therapeutics. Pharmacology
Medicine > Pharmacy and materia medica
Science > Microbiology
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Related URLs:
    Depositing user: Ms Ann Barker-Myles
    Date Deposited: 13 Oct 2009 15:10
    Last modified: 04 Sep 2014 22:42
    URI: http://strathprints.strath.ac.uk/id/eprint/13251

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