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Inflammasome Recognition and Regulation of the Legionella Flagellum

Ursula Schell1, Sylvia Simon2, Hubert Hilbi3

  • 1Max von Pettenkofer Institute, Ludwig-Maximilians University, Pettenkoferstraße 9a, 80336, Munich, Germany.

Current Topics in Microbiology and Immunology
|July 28, 2016
PubMed

Insights

The small molecule LAI-1 regulates Legionella pneumophila virulence by controlling flagellin production and motility. This quorum sensing compound coordinates bacterial invasion and host inflammasome activation, leading to Legionnaires

Area of Science:

  • Microbiology
  • Immunology
  • Bacterial Pathogenesis

Background:

  • Legionella pneumophila is a Gram-negative bacterium causing Legionnaires' disease, a severe pneumonia in humans.
  • The pathogen exhibits a biphasic life cycle, transitioning from a replicative to a virulent, motile form.
  • Virulence involves effector protein injection and formation of the Legionella-containing vacuole, alongside flagellin production.

Purpose of the Study:

  • To elucidate the regulatory mechanisms controlling Legionella pneumophila flagellin production and motility.
  • To investigate the role of the Legionella quorum sensing (Lqs) signaling compound LAI-1 in pathogen virulence.
  • To understand how LAI-1 coordinates host-pathogen interactions, including inflammasome activation.

Main Methods:

  • Analysis of the stationary phase regulatory network in L. pneumophila.
  • Investigation of nutrient availability and Lqs signaling compound LAI-1.
  • Assessment of flagellin production, motility, and inflammasome activation.

Main Results:

  • LAI-1 (3-hydroxypentadecane-4-one) was identified as a key regulator of L. pneumophila stationary phase.
  • LAI-1 coordinates flagellin production, motility, and subsequent inflammasome activation (NAIP5/NLRC4).
  • This coordination enhances bacterial virulence and facilitates host cell pyroptosis.

Conclusions:

  • The Lqs signaling compound LAI-1 is crucial for orchestrating L. pneumophila virulence.
  • LAI-1 integrates environmental cues to control bacterial motility and host immune evasion.
  • Targeting LAI-1 signaling presents a potential strategy for controlling Legionnaires' disease.
Keywords:
AmoebaAutoinducerDictyosteliumEffector proteinFlagellinMacrophageNAIP5/NLRC4 inflammasomePathogen vacuolePhosphoinositideQuorum sensingSmall GTPaseType IV secretion

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