Myco_Metabolism · How iron and manganese affect the central metabolism in pathogenic mycobacteria
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2021-06-15 → 2023-06-14
- EU contribution
- €171,473
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
How iron and manganese affect the central metabolism in pathogenic mycobacteria
Altering the availability of nutrients to starve or intoxicate pathogenic bacteria is one of the mechanisms our immune system uses to limit their replication or kill them. These nutrients include metals, elements that are essential for all cellular processes and whose intracellular concentration must be strictly controlled. Bacteria respond to these changes with specific mechanisms that allow them to survive. This project investigated the effects of iron deficiency and high manganese concentrations on the metabolism of Mycobacterium tuberculosis and Mycobacterium abscessus, two unicellular pathogenic organisms that cause lung infections. This study reveals new aspects of the physiology of two pathogenic bacteria that are highly tolerant to antibiotics. Infections caused by M. tuberculosis and M. abscessus are difficult to treat precisely because of this high tolerance. Treatment lasts from six months to two years, and is accompanied by the obvious side effects of the drugs due to the extensive therapy. M. abscessus is of a particular clinical concern as it is more tolerant than M. tuberculosis. While there are international guidelines from the WHO for the latter, M. abscessus infections are dealt with on a case-by-case basis. The nutritional conditions used in this research define a metabolic state of the bacterial cell that has never before been used to study antibiotic resistance. Such conditions may provide a new screening platform to identify new drugs or to improve existing therapies, and are applicable to all pathogenic microorganisms, not just mycobacteria.
Data: CORDIS, © European Union
Project 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).
Original text from CORDIS.
Participants
- UNIVERSITA DEGLI STUDI DI PADOVA · PadovaCoordinatorItaly
Links
- View on CORDIS
- DOI: 10.3030/101029081
- https://www.unipd.it/en/msca-individual-postdoctoral-fellowships
Data: CORDIS, © European Union