Intrabacterial lipid inclusion‐associated proteins: a core machinery conserved from saprophyte Actinobacteria to the human pathogen Mycobacterium tuberculosis

Tonia Dargham (1) , Ivy Mallick (1) , Laurent Kremer (2) , Pierre Santucci (1) , Stéphane Canaan (1)

1 LISM - Laboratoire d'ingénierie des systèmes macromoléculaires
2 IRIM - Institut de Recherche en Infectiologie de Montpellier

Mycobacterium tuberculosis (Mtb), the aetiologic agent of tuberculosis (TB), stores triacylglycerol (TAG) in the form of intrabacterial lipid inclusions (ILI) to survive and chronically persist within its host. These highly energetic molecules represent a major source of carbon to support bacterial persistence and reactivation, thus playing a leading role in TB pathogenesis. However, despite its physiological and clinical relevance, ILI metabolism in Mtb remains poorly understood. Recent discoveries have suggested that several ILI‐associated proteins might be widely conserved across TAG‐producing prokaryotes, but still very little is known regarding the nature and the biological functions of these proteins. Herein, we performed an in silico analysis of three independent ILI‐associated proteomes previously reported to computationally define a potential core ILI‐associated proteome, referred to as ILIome. Our investigation revealed the presence of 70 orthologous proteins that were strictly conserved, thereby defining a minimal ILIome core. We further narrowed our analysis to proteins involved in lipid metabolism and discuss here their putative biological functions, along with their molecular interactions and dynamics at the surface of these bacterial organelles. We also highlight the experimental limitations of the original proteomic investigations and of the present bioinformatic analysis, while describing new technological approaches and presenting biological perspectives in the field. The in silico investigation presented here aims at providing useful datasets that could constitute a scientific resource of broad interest for the mycobacterial community, with the ultimate goal of enlightening ILI metabolism in prokaryotes with a special emphasis on Mtb pathogenesis.

Domaines: Biochimie [q-bio.BM]

Tonia Dargham, Ivy Mallick, Laurent Kremer, Pierre Santucci, Stéphane Canaan. Intrabacterial lipid inclusion‐associated proteins: a core machinery conserved from saprophyte Actinobacteria to the human pathogen Mycobacterium tuberculosis. FEBS Open Bio, 2023, ⟨10.1002/2211-5463.13721⟩. ⟨hal-04291376⟩