Figure 6

Model of the modes of action of Fluspirilene and Pimozide. Both Fluspirilene and Pimozide increased the localization of Mtb in autophagy-related vesicles implying they induce selective autophagy, i.e. xenophagy (I). Although increased ROS/RNS production was significantly induced by Pimozide only, antioxidants impaired the efficacy of Pimozide and to a lesser extent also Fluspirilene (II). Fluspirilene and Pimozide both inhibited STAT5 activity and Pimozide consequently reduced CISH localization on the Mtb containing vesicle (III). Lastly, Fluspirilene and to a larger extent Pimozide, increased nuclear TFEB localization concomitant with an increased lysosomal response (IV). Black arrows indicate the general process of Mtb phagocytosis and subsequent events, white arrows show compound mediated activation or inhibition of targets and green and red lines depict signaling pathways and protein interactions with reduced or increased bacterial outgrowth as outcome, respectively.