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Imaging InlC Secretion to Investigate Cellular Infection by the Bacterial Pathogen Listeria monocytogenes
14:05

Imaging InlC Secretion to Investigate Cellular Infection by the Bacterial Pathogen Listeria monocytogenes

Published on: September 20, 2013

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Listeriolysin O allows Listeria monocytogenes replication in macrophage vacuoles

Cheryl L Birmingham1, Veronica Canadien, Natalia A Kaniuk

  • 1Cell Biology Program, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.

Nature
|January 19, 2008
PubMed

Insights

Listeria monocytogenes can replicate within host cell vacuoles during persistent infections. This novel spacious Listeria-containing phagosome (SLAP) pathway, dependent on Listeriolysin O, aids bacterial survival.

Area of Science:

  • Microbiology
  • Immunology
  • Cell Biology

Background:

  • Listeria monocytogenes is an intracellular pathogen typically replicating in host cell cytosol.
  • During persistent infection in SCID mice, L. monocytogenes was observed within vacuoles, challenging established infection paradigms.

Purpose of the Study:

  • To investigate the mechanism of L. monocytogenes vacuole occupation during persistent infection.
  • To characterize the novel spacious Listeria-containing phagosomes (SLAPs) and their role in bacterial replication and survival.

Main Methods:

  • Infection of severe combined immunodeficient (SCID) mice with L. monocytogenes.
  • In vitro cell culture experiments to observe bacterial replication and vacuole formation.
  • Immunofluorescence microscopy to identify and characterize LAMP1(+) compartments (SLAPs).
  • Analysis of bacterial replication rates in cytosol versus SLAPs.
  • Assessment of the role of Listeriolysin O (LLO) in SLAP formation and bacterial survival.

Main Results:

  • L. monocytogenes was found to replicate within non-acidic, non-degradative LAMP1(+) compartments termed SLAPs in macrophages.
  • SLAP formation is dependent on autophagy.
  • Bacterial replication rate within SLAPs is reduced compared to cytosolic replication.
  • The pore-forming toxin Listeriolysin O (LLO) is essential and sufficient for SLAP formation.
  • A low-LLO mutant showed impaired phagosome escape but slow replication in SLAPs.

Conclusions:

  • L. monocytogenes can replicate within vacuoles (SLAPs) in host macrophages during persistent infection.
  • LLO plays a crucial role in facilitating L. monocytogenes vacuolar replication and potentially establishing persistent infections.
  • This discovery reveals a new survival strategy for L. monocytogenes, distinct from its typical cytosolic replication.

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