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Effect of tyrosin phosphatases and lipid phosphatases of Leishmania parasites on the immune system of the infected host

Principal investigator
Didier Soulat

Mentor
Steffen Backert

Effect of tyrosin phosphatases and lipid phosphatases of Leishmania parasites on the immune system of the infected host

Protozoan parasites of the genus Leishmania cause a spectrum of diseases known as Leishmaniasis that range from self-healing cutaneous leishmaniasis to untreated fatal visceral leishmaniasis. Two million new cases are reported yearly and more than 350 million people, in particular immunocompromised ones are at the risk of Leishmania infection predominantly in tropical and subtropical regions. By now only few therapeutic options with even severe side-effects are available.
For some human pathogens such as the bacteria Listeria monocytogenes and Mycobacterium tuberculosis, tyrosine and phospholipid (PIP) phospatases have already been described to play a critical role during infection. Recent proteomic studies of Leishmania ssp. showed that during infection Leishmania parasites produce several proteins with phosphatase activity. On one side, Leishmania parasites express proteins which have a strong homology with PIP phosphatases previously characterized as virulence factors. On the other side, the parasite can secrete a protein, Lp1, that structurally resembles to Protein Tyrosine Phosphatase (PTP). Strikingly, this secreted phosphatase is homologous to the human phosphatase PRL-1 that has an important function in the regulation of cellular growth.
Considering the crucial role of tyrosine phosphorylation within the post-translational regulation of cell metabolism, we hypothesize that the leishmanian phosphatase Lp1 could play an important role for the parasites` virulence. Main objectives of the project will be to functionally characterize four tyrosine and lipid phosphatases, focusing on the Lp1 candidate. The investigation will address the phosphatases` presumed role as new virulence factors during infection. The study of these phosphatases will lead to a better understanding of the parasites' immune evasion strategies and may even represent a new target for more specific therapy.

Figure: Crystal structure of the Leishmania phosphatase Lp1 (blue) compared to the human phosphatase PRL-1 (orange), overlay on the right

 

Publications

 

Presentations

October 2015 2nd International SFB 796 Conference: Mechanisms of microbial host cell manipulation: From plants to humans, Erlangen, Germany
”Effect of secreted tyrosine phosphatases from Leishmania parasites on the immune system of infected hosts”
Poster
     
July 2015 7th Annual Retreat, Erlangen School of Molecular Communication, Schloss Hirschberg, Beilngries, Germany
”Effect of secreted tyrosine phosphatases from Leishmania parasites on the immune system of infected hosts”
Talk
     
Februar 2015 Status workshop of the DGHM special interest group Eukaryotic Pathogens
”Effect of secreted tyrosine phosphatases from Leishmania parasites on the immune system of infected hosts”
Talk
     
July 2014 6th Annual Retreat, Erlangen School of Molecular Communication, Kloster Banz, Bad Staffelstein, Germany
“Effect of tyrosine phosphatases from Leishmania parasites on the immune system of infected hosts”
Talk
     
März 2014

18. Symposium "Infektion und Immunabwehr", Burg Rothenfels, Germany
“Effect of tyrosine phosphatases from Leishmania parasites on the immune system of infected hosts”

Talk
     
July 2013 5th Annual Retreat, Erlangen School of Molecular Communication, Kloster Banz, Bad Staffelstein, Germany
Effect of tyrosine phosphatases and lipid phosphatases of Leishmania parasites on the immune system of infected hosts
Talk