The Mycobacterium marinum ESX-1 system mediates phagosomal permeabilization and type I interferon production via separable mechanisms

Significance The mycobacterial ESX-1 type VII secretion system promotes phagosomal rupture and type I IFN production, key features of tuberculosis pathogenesis. It is currently believed that the secreted substrate ESAT-6 is required for phagosomal permeabilization and that a subsequent leakage of bacterial DNA into the host cell cytosol triggers type I IFN. Our genetic analyses demonstrate that ESX-1–mediated membrane permeabilization does not...