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Mycobacterial Acid Tolerance Enables Phagolysosomal Survival and Establishment of Tuberculous Infection In Vivo.

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Levitte, Steven 
Adams, Kristin N 
Berg, Russell D 
Cosma, Christine L 
Urdahl, Kevin B 


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 avoidance strategies to rapidly deliver a substantial proportion of infecting bacteria to phagolysosomes. Exploiting the optical transparency of the zebrafish, we tracked the fates of individual mycobacteria delivered to phagosomes versus phagolysosomes and discovered that bacteria survive and grow in phagolysosomes, though growth is slower. MarP is required specifically for phagolysosomal survival, making it an important determinant for the establishment of mycobacterial infection in their hosts. Our work suggests that if pathogenic mycobacteria fail to prevent lysosomal trafficking, they tolerate the resulting acidic environment of the phagolysosome to establish infection.



Animals, Anti-Bacterial Agents, Bacterial Proteins, Carboxylic Acids, Cells, Cultured, Disease Models, Animal, Host-Pathogen Interactions, Lysosomes, Macrophages, Mice, Inbred C57BL, Microbial Viability, Mycobacterium Infections, Nontuberculous, Mycobacterium marinum, Stress, Physiological, Virulence Factors, Zebrafish

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Cell Host Microbe

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Elsevier BV
Wellcome Trust (103950/Z/14/Z)
National Institutes of Health (Grant IDs: R37AI054503, R01 AI076327, 5T32HD007233, 5F30HL110455), Wellcome Trust, National Institute of Health Research Cambridge Biomedical Research Centre