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The blockade of phagolysosomal fusion is considered a critical mycobacterial strategy to survive in macrophages. However, viable mycobacteria have been observed in phagolysosomes during infection of cultured macrophages, and mycobacteria have the virulence determinant MarP, which confers acid resistance in vitro. Here we show in mice and zebrafish that innate macrophages overcome mycobacterial lysosomal...
A zebrafish genetic screen for determinants of susceptibility to Mycobacterium marinum identified a hypersusceptible mutant deficient in lysosomal cysteine cathepsins that manifests hallmarks of human lysosomal storage diseases. Under homeostatic conditions, mutant macrophages accumulate undigested lysosomal material, which disrupts endocytic recycling and impairs their migration to, and thus engulfment...
Mycobacterium tuberculosis (MTB) continues to plague humanity because of significant gaps in our understanding of MTB infection, including the nature of a protective versus pathological host response, why antimicrobial cure is so difficult, and the ineffectiveness of vaccination. The development of a zebrafish model, utilizing infection with the natural fish pathogen Mycobacterium marinum (Mm), has...
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