Mycobacterium-Host Screening Identifies Novel Lysosomal Escape Pathways

This dataset explores intracellular survival mechanisms of Mycobacterium leprae. Using clinical lesion proteomics, we identified 14 highly expressed T7SS effectors. Genome-wide yeast two-/three-hybrid screening against a macrophage interactome revealed 132 host targets and mapped the first global M. leprae effector–host interaction network. Functional validation defined two conserved lysosomal escape pathways: PPE68–Coro1A preventing phagosome–lysosome fusion, and EsxA–EsxB–CCDC115 disrupting V-ATPase assembly. Comparative M. marinum models confirmed their essential role in survival and pathogenesis. The dataset includes proteomic profiles, interaction matrices, and validation assays, which can be used to investigate host–pathogen interactions and identify therapeutic targets.