PDIM drives the transition from repairable to catastrophic EsxA-mediated vacuole membrane damage during Mycobacterium marinum infection.

PDIM amplifies EsxA-induced vacuole membrane damage, promoting catastrophic rupture and bacterial escape during Mycobacterium marinum infection.

• Why it matters: Understanding how mycobacteria transition from repairable to catastrophic vacuole damage is crucial for revealing mechanisms of bacterial dissemination and pathogenicity, which are not well understood.
• What they did: The study used host membrane damage and repair reporters, along with single and double bacterial mutants, to analyze the roles of EsxA/EsxB and PDIM during infection of Dictyostelium discoideum and murine microglial cells, focusing on stages of vacuole damage.
• The result: PDIM-deficient bacteria showed reduced autophagy repair and remained within the vacuole, but disrupting host autophagy increased bacterial escape, indicating PDIM's role in amplifying damage; the findings support a two-step model where EsxA initiates damage and PDIM drives rupture.