PUBLICATION

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

Authors
Levitte, S., Adams, K.N., Berg, R.D., Cosma, C.L., Urdahl, K.B., Ramakrishnan, L.
ID
ZDB-PUB-160812-3
Date
2016
Source
Cell Host & Microbe   20: 250-258 (Journal)
Registered Authors
Adams, Kristin, Berg, Russell, Cosma, Christine, Ramakrishnan, Lalita
Keywords
none
MeSH Terms
  • Host-Pathogen Interactions
  • Carboxylic Acids/metabolism*
  • Disease Models, Animal
  • Mice, Inbred C57BL
  • Bacterial Proteins/genetics
  • Bacterial Proteins/metabolism
  • Mycobacterium marinum/drug effects
  • Mycobacterium marinum/growth & development
  • Mycobacterium marinum/physiology*
  • Macrophages/microbiology*
  • Zebrafish
  • Microbial Viability/drug effects*
  • Stress, Physiological*
  • Virulence Factors/genetics
  • Virulence Factors/metabolism
  • Animals
  • Anti-Bacterial Agents/metabolism*
  • Cells, Cultured
  • Lysosomes/microbiology*
  • Mycobacterium Infections, Nontuberculous/microbiology
(all 20)
PubMed
27512905 Full text @ Cell Host Microbe
Abstract
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.
Genes / Markers
Figures
Figure Gallery (3 images)
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
t26683
    		Point Mutation
    w200TgTransgenic Insertion
      1 - 2 of 2
      Show
      Human Disease / Model
      Human Disease Fish Conditions Evidence
      bacterial infectious diseaseTAS
      tuberculosisTAS
      1 - 2 of 2
      Show
      Sequence Targeting Reagents
      Target Reagent Reagent Type
      atp6v1aaMO1-atp6v1aaMRPHLNO
      ifng1MO1-ifng1MRPHLNO
      ifng1rMO1-ifng1rMRPHLNO
      ifngr1MO2-ifngr1MRPHLNO
      tnfrsf1aMO2-tnfrsf1aMRPHLNO
      1 - 5 of 5
      Show
      Fish
      No data available
      Antibodies
      No data available
      Orthology
      No data available
      Engineered Foreign Genes
      Marker Marker Type Name
      YFPEFGYFP
      1 - 1 of 1
      Show
      Mapping
      No data available
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      Citation
      Levitte, S., Adams, K.N., Berg, R.D., Cosma, C.L., Urdahl, K.B., Ramakrishnan, L. (2016) Mycobacterial Acid Tolerance Enables Phagolysosomal Survival and Establishment of Tuberculous Infection In Vivo. Cell Host & Microbe. 20:250-258.