Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2023.04.17.537276v1?rss=1

Authors: Anand, A., Mazur, A.-C., Rosell-Arevalo, P., Franzkoch, R., Breitsprecher, L., Listian, S. A., Hüttel, S. V., Müller, D., Schäfer, D. G., Vormittag, S., Hilbi, H., Maniak, M., Gutierrez, M., Barisch, C.

Abstract:
Several intracellular pathogens, such as Mycobacterium tuberculosis, damage endomembranes to access the cytosol and subvert innate immune responses. The host counteracts endomembrane damage by recruiting repair machineries that retain the pathogen inside the vacuole. Here, we show that the endoplasmic reticulum (ER)-Golgi protein oxysterol binding protein (OSBP) and its Dictyostelium discoideum homologue OSBP8 are recruited to the Mycobacterium-containing vacuole (MCV) after ESX-1-dependent membrane damage. Lack of OSBP8 causes a hyperaccumulation of phosphatidylinositol-4-phosphate (PI4P) on the MCV and decreased cell viability. OSBP8-depleted cells had reduced lysosomal and degradative capabilities of their vacuoles that favoured mycobacterial growth. In agreement with a function of OSBP8 in membrane repair, human macrophages infected with M. tuberculosis recruited OSBP in an ESX-1 dependent manner. These findings identified an ER-dependent repair mechanism for restoring MCVs in which OSBP8 functions to equilibrate PI4P levels on damaged membranes.

Copy rights belong to original authors. Visit the link for more info

Podcast created by Paper Player, LLC