Lipid droplet-associated proteins are involved in the biosynthesis and hydrolysis of triacylglycerol in Mycobacterium bovis bacillus Calmette-Guerin.

摘要: Mycobacteria store triacylglycerols (TGs) in the form of intracellular lipid droplets (LDs) during hypoxia-induced nonreplicating persistence. These bacteria are phenotypically drug-resistant and therefore believed to be cause for prolonged tuberculosis treatment. LDs also associated with bacilli patient sputum hypervirulent strains. Although proteins bound well characterized eukaryotes, identities functions such have not been described mycobacteria. Here, we identified five proteins: Tgs1 (BCG3153c), Tgs2 (BCG3794c), BCG1169c, BCG1489c, BCG1721, which exclusively purified from hypoxic Mycobacterium bovis bacillus Calmette-Guerin (BCG). Disruption genes tgs1, tgs2, BCG1489c M. BCG revealed that they indeed involved TG metabolism. We an essential bi-functional enzyme capable promoting buildup hydrolysis TGs, depending on metabolic state. Nonreplicating mycobacteria overexpressing a BCG1721 construct inactive lipase domain displayed phenotype attenuated breakdown regrowth upon resuscitation. In addition, by heterologous expression baker's yeast, these mycobacterial co-localized complemented lipase-deficient yeast strain, indicating neutral deposition homeostasis eukaryotic prokaryotic microorganisms functionally related. The demonstrated functional role support growth resuscitation makes this novel LD-associated factor potential new target therapeutic intervention.