PATHO IRON · Cytosolic iron metabolism in unicellular eukaryotic pathogens
FP7 — People (Marie Curie Actions)
- Duration
- 2008-08-04 → 2010-02-03
- EU contribution
- €133,662
- Participants
- 1
- Scheme
- MC-IEF
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Results in brief
Cytosolic iron metabolism in unicellular eukaryotic pathogens
Iron is an essential nutrient for virtually all living organisms and host iron availability plays a critical role in the host-pathogen relationship. However, our knowledge about iron metabolism in eukaryotic pathogenic microorganisms is poor; it is not known, how iron is stored in the cell or how it is utilised. This project was focused on iron metabolism in different unicellular microorganisms such as Trichomonas vaginalis and Candida albicans. In these organisms we have found out that unlike in different cellular organelles, cytosolic iron is present in a non-protein bound form. Such new insights are not only important in their own right but may lead to new chemotherapeutic strategies. During the tenure of the project, an international collaboration was initiated focused on a recently discovered photosynthetic marine microorganism Chromera velia. We have described in C. velia cells a novel two-step model of iron uptake in which aqueous ferric ions are first concentrated in the cell wall before being taken up by the cells without prior reduction, by a thermodynamically controlled mechanism. It is of particular interest to elucidate the molecular mechanisms underlying acquisition of iron by marine phytoplankton and our results may help to determine which iron sources are preferentially assimilated with regard to the yield of carbon fixation. Moreover, C. velia is closely related to Apicomplexan parasites including the causative agent of malaria. Our investigation of biochemical processes of C. velia will help us to understand how photosynthetic algae evolved into the fully parasitic Apicomplexa and may lead to new therapeutic strategies.
Data: CORDIS, © European Union
Project objective
Iron is an essential nutrient for virtually all living organisms and host iron availability plays a critical role in the host–pathogen relationship. Without effective mechanisms for acquisition, transport and utilization of iron, no organism especially parasites with high iron requirements, can survive. However, our knowledge about intracellular iron metabolism in eukaryotic pathogenic microorganisms is poor; it is not known, how iron is stored in the cell or how it is utilized. In the proposed project, we will investigate cytosolic iron metabolism in three unicellular eukaryotic pathogens: Candida albicans, Trichomonas vaginalis and Giardia intestinalis. We will use two different proteomic methods to identify proteins involved in iron metabolism: 1) 2D gel electrophoresis of cytosolic fractions from cells grown under iron-rich and iron-restricted conditions and 2) separation of 55Fe radiolabeled cytosolic iron complexes by liquid chromatography followed by native electrophoresis. Obtained proteins/protein complexes will be identified by Matrix-assisted laser desorption/ionization mass spectrometry and liquid chromatography-tandem mass spectrometry. We will test the cellular localization and the effect of the identified proteins on iron metabolism by overexpression in pathogens and yeast. The project has great potential to discover new mechanisms of iron metabolism as well as identify new therapeutic approaches for the treatment of human pathogens. This multidisciplinary project investigating different pathogenic organisms and using a broad range of state-of-the-art techniques and approaches will allow a young researcher with outstanding track record and potential to return to Europe, integrate into European scientific community, consolidate his research maturity and provide him with a strong background for establishing his own laboratory in later stages of his career.
Original text from CORDIS.
Participants
- CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS · ParisCoordinatorFrance
Links
Data: CORDIS, © European Union