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Molecular characterisation of the intracellular habitat of Leishmania spp. in view of the development of new vaccination and therapy approaches

Infections with unicellular parasites of the genus Leishmania cause a range of diseases which include self-healing skin lesions and systemic infections that can be lethal if untreated. The parasites are transmitted by blood-sucking sandflies that are endemic to the Mediterranean region as well as the Middle and Near East, the Indian sub-continent and Central and South America.

Scanning EM micrographMacrophage in process of phagocytosing a L. major promastigote. Source: Source: V. Brinkmann, MPI f. Infektionsbiologie, Berlin

In Germany transmission has only been reported from a few individual cases so far. Most leishmaniases are diagnosed in returning travelers or in personnel of the armed forces or other organizations who had been stationed in endemic regions. There is currently no vaccination against these infections and therapy by drug treatment can be difficult. The long-term goal of our investigations is to advance the development of new intervention strategies, in particular vaccines against these parasites.

The parasites thrive in phagocytes, such as macrophages and dendritic cells. We have developed a new method to enrich and purify the habitat of these intracellular pathogens for proteome analyses. This compartment is similar to a phagolysosome of which we were able to define a molecular inventory.

At present in a project supported by DFG (German Research Foundation), we investigate on a molecular level the habitat components that are important for the multiplication of the parasites. This will allow to test whether interfering with these factors is possible and whether leads to new strategies for drug and vaccine developments can thus be identified.

Co-worker:

  • Geo Semini
  • Diego Peres-Alonso
  • Petra Gosten Heinrich

Date: 30.10.2014

Publications

  • Maroof A, Brown N, Smith B, Hodgkinson MR, Maxwell A, Losch FO, Fritz U, Walden P, Lacey CN, Smith DF, Aebischer T, Kaye PM (2012): Therapeutic vaccination with recombinant adenovirus reduces splenic parasite burden in experimental visceral leishmaniasis.
    J. Infect. Dis. 205 (5): 853-863. Epub Feb 1. doi: 10.1093/infdis/jir842. more

  • Schroeder J, Brown N, Kaye P, Aebischer T (2011): Single Dose Novel Salmonella Vaccine Enhances Resistance against Visceralizing L. major and L. donovani Infection in Susceptible BALB/c Mice.
    PLoS Negl. Trop. Dis. 5 (12): e1406. Epub Dec 27. doi:10.1371/journal.pntd.0001406. more

  • Paape D, Barrios-Llerena ME, Le Bihan T, Mackay L, Aebischer T (2010): Gel free analysis of the proteome of intracellular Leishmania mexicana.
    Mol. Biochem. Parasitol. 169 (2): 108-114. Epub 2009 Nov 10. doi:10.1016/j.molbiopara.2009.10.009. more

  • Lippuner C, Paape D, Paterou A, Brand J, Richardson M, Smith AJ, Hoffmann K, Brinkmann V, Blackburn C, Aebischer T (2008): Real-time imaging of Leishmania mexicana-infected early phagosomes: a study using primary macrophages generated from green fluorescent protein-Rab5 transgenic mice.
    FASEB J. 23 (2): 483-491. Epub 2008 Oct 16. more

  • Paape D, Lippuner C, Schmid M, Ackermann R, Barrios-Llerena ME, Zimny-Arndt U, Brinkmann V, Arndt B, Pleissner KP, Jungblut PR, Aebischer T (2008): Transgenic, fluorescent Leishmania mexicana allow direct analysis of the proteome of intracellular amastigotes.
    Mol. Cell. Proteomics 7 (9): 1688-1701. Epub 2008 May 12. more