Membrane-dependent actin polymerization mediated by the Legionella pneumophila effector protein MavH

Qing Zhang1,2, Min Wan1,2, Elena Kudryashova3

  • 1Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, New York, United States of America.

Plos Pathogens
|July 18, 2023
PubMed

Insights

Legionella MavH effector protein remodels host actin cytoskeleton, promoting bacterial entry into cells. This mechanism involves actin assembly and membrane tubulation, crucial for early infection stages.

Area of Science:

  • Microbiology
  • Cell Biology
  • Biochemistry

Background:

  • Legionella pneumophila (L. pneumophila) infects eukaryotic cells within a Legionella-containing vacuole (LCV).
  • Over 330 effector proteins delivered via type IV secretion system control L. pneumophila infection.
  • Host cell actin dynamics are critical for intracellular bacterial pathogen survival.

Purpose of the Study:

  • To investigate the function of the Legionella effector protein MavH.
  • To elucidate the mechanism by which MavH influences host cell actin cytoskeleton and membrane dynamics.
  • To determine MavH's role in the early stages of L. pneumophila infection.

Main Methods:

  • Ectopic expression of MavH in eukaryotic cells.
  • Confocal microscopy to analyze MavH localization and actin remodeling.
  • In vitro liposome-based assays to study actin assembly and membrane tubulation.
  • Biochemical assays to identify protein interaction domains.

Main Results:

  • MavH localizes to endosomes and remodels actin cytoskeleton in a phosphatidylinositol 3-phosphate (PI(3)P)-dependent manner.
  • MavH recruits host actin capping protein (CP) and actin via its CPI motif and WH2-like domain.
  • MavH stimulates actin assembly on PI(3)P liposomes, inducing membrane tubulation and negatively regulating F-actin density.
  • MavH is recruited to the LCV during early infection and facilitates bacterial entry.

Conclusions:

  • MavH utilizes a novel mechanism of membrane tubulation through PI(3)P-dependent actin polymerization.
  • MavH regulates host actin dynamics to facilitate L. pneumophila entry into host cells.
  • MavH plays a significant role in the early pathogenesis of L. pneumophila infection.

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