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Selection of new therapeutic targets in relation to lipid metabolism in Mycobacterium abscessus
Thèses et HDR   Open Access

Selection of new therapeutic targets in relation to lipid metabolism in Mycobacterium abscessus

Tonia Dargham
Doctoral, Université de Montpellier
10/04/2024

Résumé

lipid metabolism lipid metabolism bacterial lipid droplets proximity labelling proteome therapeutic targets intrabacterial lipid inclusions lipid metabolism. APEX2 Mycobacterium abscessus Mycobacterium abscessus inclusions lipidiques intrabactériennes APEX2 protéome cibles thérapeutiques métabolisme lipidique Mycobacterium abscessus persistence mycobacteria ILI-associated proteins proteomic pathogenesis triacylglycerol ILI
Lipid droplets are conserved organelles in a large number of organisms, playing an essential role in energy storage and membrane renewal. Among prokaryotes, actinobacteria, notably the genus mycobacterium, are known for their ability to accumulate triacylglycerols in the form of intrabacterial lipid inclusions (ILIs). In addition to their role as a carbon source, ILIs are involved in antibiotic tolerance, persistence and virulence. These organelles are surrounded by a phospholipid monolayer to which proteins are anchored. Despite recent studies on the ILI proteome, little is known about the main protein players in M. tuberculosis and M. abscessus, two pathogens responsible for lung infections in humans. In this context, my thesis focused on identifying the ILI proteome during synthesis and degradation in M. abscessus. Using a reversible in vitro model developed in the laboratory, coupled with an APEX2 proximity labeling technique and mass spectrometry, I was able to identify the proteins that would be present on the surface of these ILI during their synthesis and degradation. I was also able to show that this was a dynamic process involving protein exchanges depending on ILI size. Finally, I validated some of my results and determined the involvement of a few proteins in the biogenesis of these ILIs. During my thesis, only a part of the results I generated could be exploited, but the data set (ILI biogenesis and degradation), once validated, could open up new perspectives on the physiological role of these proteins as potential therapeutic targets for countering the persistence of mycobacteria.

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