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The formation of mycobacterial lipid bodies and their role in antibiotic resistance

Funder: Netherlands Organisation for Scientific Research (NWO)Project code: 016.Veni.171.088

The formation of mycobacterial lipid bodies and their role in antibiotic resistance

Description

Mycobacterium tuberculosis causes tuberculosis, a chronic and wasting disease. Although almost forgotten in the Western world, this disease still takes the lives of nearly 1.5 million humans every year. One of the characteristics of this disease is that an M. tuberculosis infection can go unnoticed for decades. Such a latent infection can reactivate and lead to active disease later in life. During such a latent infection, M. tuberculosis withstands host-derived attacks by forming so-called persister cells. These persisters are characterized by a non- (or slowly-) dividing, drug resistant phenotype, which makes them challenging to treat. One of the hallmarks of persister cells is the presence of intracellular lipid bodies which are produced using host-derived lipids. The goal of this project is to decipher the mechanism of mycobacterial lipid body formation and unravel the role of these structures in persister cell formation and functioning. The following topics will be studied: processing of host-derived lipids, uptake of processed lipid products, storage of lipid products and the role of lipid bodies in antibiotic resistance. I will study lipid body formation by combining state-of-the-art post-genomic sequencing techniques with bacterial cell sorting. Understanding lipid body formation will lead to new strategies to target and treat persister cell populations.

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