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Method for the Isolation of Francisella tularensis Outer Membranes
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Method for the Isolation of Francisella tularensis Outer Membranes

Published on: June 29, 2010

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Host glycosylation pathways and the unfolded protein response contribute to the infection by Francisella

Monique Barel1,2, Anne Harduin-Lepers3,4, Lucie Portier3,4

  • 1Université Paris Descartes, Sorbonne Paris Cité, Paris, France.

Cellular Microbiology
|May 18, 2016
PubMed

Insights

Francisella tularensis infection alters protein glycosylation in human macrophages, increasing O-glycosylation of the BiP chaperone. This impacts bacterial multiplication and host cell response.

Area of Science:

  • Microbiology
  • Cell Biology
  • Immunology

Background:

  • Protein glycosylation is vital for cellular functions.
  • Francisella tularensis infection causes rapid deglycosylation of macrophage membrane proteins.
  • The bacterium modulates host cell gene expression related to glycosylation.

Purpose of the Study:

  • Investigate the impact of Francisella tularensis infection on protein glycosylation in human macrophages.
  • Identify specific glycosylated proteins affected by the infection.
  • Determine the role of the endoplasmic reticulum chaperone BiP in bacterial pathogenesis.

Main Methods:

  • Glycan processing gene microarray analysis.
  • Lectin and Western blotting of infected macrophage cell extracts.
  • Mass spectrometry to identify O-glycosylated proteins.
  • Biochemical assays to assess Unfolded Protein Response (UPR) activation.

Main Results:

  • Francisella infection modulated numerous glycosidase and glycosyltransferase genes.
  • Increased N- and O-protein glycosylation was observed in infected macrophages.
  • BiP (HSPA5/GRP78) was identified as an O-glycosylated protein modulated by the infection.
  • BiP expression was essential for Francisella intracellular multiplication.
  • Francisella differentially modulated BiP-dependent activation of UPR proteins (IRE1, PERK, ATF6).

Conclusions:

  • Francisella tularensis manipulates host cell protein glycosylation, including O-glycosylation of BiP.
  • BiP plays a critical role in supporting intracellular bacterial growth.
  • The pathogen likely exploits the Unfolded Protein Response (UPR) pathway for adaptation and survival within host cells.

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