Mycobacterial Acid Tolerance Enables Phagolysosomal Survival and Establishment of Tuberculous Infection In Vivo.
|Title||Mycobacterial Acid Tolerance Enables Phagolysosomal Survival and Establishment of Tuberculous Infection In Vivo.|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Levitte S, Adams KN, Berg RD, Cosma CL, Urdahl KB, Ramakrishnan L|
|Journal||Cell Host Microbe|
|Date Published||2016 Aug 10|
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.
|Alternate Journal||Cell Host Microbe|
|PubMed Central ID||PMC4985559|
|Grant List||F30 HL110455 / HL / NHLBI NIH HHS / United States |
T32 HD007233 / HD / NICHD NIH HHS / United States
R01 AI076327 / AI / NIAID NIH HHS / United States
T32 GM007266 / GM / NIGMS NIH HHS / United States
U19 AI106761 / AI / NIAID NIH HHS / United States
R37 AI054503 / AI / NIAID NIH HHS / United States