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How iron and manganese affect the central metabolism in pathogenic mycobacteria

Project description

The role of metals in bacterial virulence

Hosts have evolved several mechanisms to counteract bacterial infection. One of them is to restrict nutrient availability, which is central for pathogen survival, fitness and virulence. Immune cells such as macrophages and neutrophils achieve this by limiting access to metals such as iron and manganese that are necessary for the function of key metabolic enzymes. The scope of the EU-funded Myco_Metabolism project is to investigate how metal availability impacts the overall metabolism of Mycobacteria species. Results will unveil unknown aspects of mycobacterial physiology and identify new targets for therapeutic intervention.

Objective

I aim to define how Mycobacterium tuberculosis (Mtb) and Mycobacterium abscessus (Mabs) have adapted their central metabolism (CM) to variation of metals availability. Bacterial nutrition is a fundamental aspect of pathogenesis. While the host environment is in principle nutrient-rich, hosts have evolved strategies to interfere with nutrient-acquisition by pathogens. Pathogens, in turn, have developed mechanisms to circumvent these restrictions. The ability to adapt to nutrient availability drives the fitness of pathogen, influencing the outcome of infection. One of the strategies adopted by innate immune cells such as macrophages and neutrophils to limit bacterial replication is varying the availability of metals, starving or intoxicating the unwelcome guest.
The expression and the activity of some central metabolism enzymes are regulated by metal availability in pathogenic bacteria, and it is unknown how this regulation affects the assimilation of carbon sources. Preliminary data shows that Fe and Mn affect the carbon sources metabolism in these pathogens. I aim to identify potential Fe or Mn-regulated metabolic routes utilising proteomics (LC-MS/MS) and metabolomics (LC-MS). These investigations will help to elucidate a neglected aspect of mycobacterial physiology, the interaction between metal homeostasis and central metabolism, disclosing more mechanisms underlying the mycobacteria physiology.
Through this EF, I will bring the knowledge acquired during my five-year appointment at the Francis Crick Institute (UK) (mycobacterial metabolism and metabolomics) to my origin country (Italy) implementing my research line at the University of Padua. Through this EF, I will undertake training to re-enforce my independence, increase my expertise in proteomics (at the UNIPD) and metabolomics (at the secondment, Francis Crick).

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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(opens in new window) H2020-MSCA-IF-2020

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Coordinator

UNIVERSITA DEGLI STUDI DI PADOVA
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 171 473,28
Address
VIA 8 FEBBRAIO 2
35122 PADOVA
Italy

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Region
Nord-Est Veneto Padova
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 171 473,28
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