Listeriolysin O activates mitogen-activated protein kinase in eucaryotic cells

P Tang1, I Rosenshine, P Cossart

  • 1Biotechnology Laboratory, Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, Canada.

Insights

Listeria monocytogenes infection activates mitogen-activated protein (MAP) kinase via listeriolysin O (LLO). This bacterial toxin permeabilizes host cells, leading to MAP kinase activation, independent of bacterial invasion.

Area of Science:

  • Microbiology
  • Cell Biology
  • Molecular Biology

Background:

  • Infection with Listeria monocytogenes is known to activate mitogen-activated protein (MAP) kinase.
  • The specific bacterial factor responsible for this activation was not previously identified.

Purpose of the Study:

  • To identify the bacterial factor from Listeria monocytogenes that activates MAP kinase.
  • To elucidate the mechanism by which this factor induces MAP kinase activation.

Main Methods:

  • Analysis of various Listeria monocytogenes mutants.
  • Treatment of HeLa cells with purified listeriolysin O (LLO) and its mutants.
  • Assessment of MAP kinase tyrosine phosphorylation.
  • Comparison with other pore-forming agents like streptolysin O and saponin.

Main Results:

  • Listeriolysin O (LLO) was identified as the bacterial factor responsible for MAP kinase activation.
  • LLO, either in growth supernatant or purified form, induced MAP kinase tyrosine phosphorylation in HeLa cells.
  • LLO mutations reducing cytolytic activity, but not membrane binding, diminished MAP kinase activation.
  • Other pore-forming agents, streptolysin O and saponin, also activated MAP kinase.

Conclusions:

  • MAP kinase activation during Listeria monocytogenes infection is primarily mediated by the pore-forming activity of LLO.
  • The observed MAP kinase activation is likely a consequence of host cell membrane permeabilization by LLO.
  • This activation mechanism may be independent of the bacterial invasion process.

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