TitleMycobacterium tuberculosis ( Mtb) lipid mediated lysosomal rewiring in infected macrophages modulates intracellular Mtb trafficking and survival
Publication TypeJournal Article
Year of Publication2020
AuthorsSachdeva K, Goel M, Sudhakar M, Mehta M, Raju R, Raman K, Singh A, Sundaramurthy V
JournalJ Biol Chem
Date Published2020 Jul 03

Intracellular pathogens commonly manipulate the host lysosomal system for their survival. However, whether this pathogen-induced alteration affects the organization and functioning of the lysosomal system itself is not known. Here, using and infections and quantitative image analysis, we show that the lysosomal content and activity are globally elevated in ()-infected macrophages. We observed that this enhanced lysosomal state is sustained over time and defines an adaptive homeostasis in the infected macrophage. Lysosomal alterations are caused by mycobacterial surface components, notably the cell wall-associated lipid sulfolipid-1 (SL-1), which functions through the mTOR complex 1 (mTORC1)-transcription factor EB (TFEB) axis in the host cells. An mutant lacking SL-1, Δ shows attenuated lysosomal rewiring compared with the WT in both and infections. Exposing macrophages to purified SL-1 enhanced the trafficking of phagocytic cargo to lysosomes. Correspondingly, Δ exhibited a further reduction in lysosomal delivery compared with the WT. Reduced trafficking of this mutant strain to lysosomes correlated with enhanced intracellular bacterial survival. Our results reveal that global alteration of the host lysosomal system is a defining feature of -infected macrophages and suggest that this altered lysosomal state protects host cell integrity and contributes to the containment of the pathogen.

Alternate JournalJ. Biol. Chem.
PubMed ID32424041
PubMed Central IDPMC7335774