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The autophagic machinery ensures nonlytic transmission of mycobacteria

Lilli Gerstenmaier1, Rachel Pilla1, Lydia Herrmann1

  • 1Section Parasitology, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany;

Proceedings of the National Academy of Sciences of the United States of America
|February 4, 2015
PubMed

Insights

Pathogenic mycobacteria use a unique autophagocytic vacuole to spread between cells without lysis. Impairing autophagy blocks this bacterial transmission and causes host cell death, revealing a novel host-pathogen interaction.

Area of Science:

  • Cell Biology
  • Microbiology
  • Immunology

Background:

  • Bacterial egress and cell-to-cell transmission mechanisms are poorly understood, unlike pathogen uptake.
  • Pathogenic mycobacteria utilize a nonlytic ejection mechanism involving an F-actin ejectosome for transmission between phagocytic cells.

Purpose of the Study:

  • To investigate how host cells maintain plasma membrane integrity during bacterial ejection.
  • To elucidate the role of the autophagic machinery in the nonlytic spreading of bacteria.

Main Methods:

  • Microscopy and live-cell imaging to observe bacterial-host cell interactions.
  • Genetic manipulation to impair the autophagic pathway in host cells.
  • Assessment of host cell viability and plasma membrane integrity.

Main Results:

  • Ejecting mycobacteria are associated with a distinct polar autophagocytic vacuole.
  • Impairment of autophagy significantly inhibits bacterial cell-to-cell transmission.
  • Disruption of autophagy leads to host plasma membrane compromise and cell death.

Conclusions:

  • The autophagic machinery plays a critical, previously unrecognized role in nonlytic bacterial egress.
  • A highly ordered interaction exists between mycobacteria and the autophagic pathway for cell-to-cell transmission.
  • This interaction may represent an ancient mechanism for ensuring nonlytic bacterial spreading.
Keywords:
Dictyostelium discoideumMycobacterium marinumautophagyejection

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