USP8 coordinates ESCRT-mediated membrane repair, xenophagy, and oxidative stress responses during Mycobacterium tuberculosis infection

We show that USP8 colocalizes with intracellular Mtb, recognizes phagosomal membrane damage, and is required for ESCRT-dependent membrane repair. Furthermore, USP8 regulates the NRF2-dependent antioxidant signature. Taken together, our study shows a central role of USP8 in promoting intracellular growth of Mtb by coordinating phagosomal membrane repair, ubiquitin-driven selective autophagy, and the oxidative stress response. Overall design: BMDMs were seeded at E6 cells per well in a 6-well -plate and transfected with scrambled or Usp8 siRNA at 50nM. 2 days later the samples were either not infected or infected with H37Rv at MOI 5 for 24 and 72 h. RNA was prepared using the Direct-Zol RNA Mini-Prep kit. Each sample had 6 replicates.