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Updated: Nov 18, 2025

Invasion of Human Cells by a Bacterial Pathogen
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Invasion of Human Cells by a Bacterial Pathogen

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The Gb3-enriched CD59/flotillin plasma membrane domain regulates host cell invasion by Pseudomonas aeruginosa

Annette Brandel1,2,3, Sahaja Aigal1,2,4, Simon Lagies1,5,6

  • 1Faculty of Biology, University of Freiburg, Schänzlestraße 1, 79104, Freiburg, Germany.

Cellular and Molecular Life Sciences : CMLS
|February 8, 2021
PubMed

Insights

Pseudomonas aeruginosa invasion involves the bacterial lectin LecA binding to host cell globotriaosylceramide (Gb3). This interaction forms a membrane domain that facilitates bacterial uptake, highlighting a new target for combating infections.

Area of Science:

  • Microbiology
  • Cell Biology
  • Biochemistry

Background:

  • Pseudomonas aeruginosa is an opportunistic pathogen known for antibiotic resistance.
  • The bacterial lectin LecA and host cell globotriaosylceramide (Gb3) interaction is key for P. aeruginosa engulfment.
  • Understanding host-pathogen interactions is crucial for developing new therapeutic strategies.

Purpose of the Study:

  • To define the host cell membrane domain associated with the bacterial lectin LecA.
  • To elucidate the molecular mechanisms underlying P. aeruginosa invasion mediated by LecA-Gb3 interaction.
  • To identify host cell proteins involved in facilitating bacterial uptake.

Main Methods:

  • Pull-down assays and mass spectrometry to identify LecA-associated membrane proteins.
  • Analysis of Gb3 species preference for LecA binding.
  • Investigating the role of phosphatidylinositol (3,4,5)-trisphosphate (PIP3) clusters and host proteins (flotillins, CD59) in bacterial invasion.
  • Depletion studies to assess the impact of host protein absence on P. aeruginosa invasiveness.

Main Results:

  • LecA preferentially binds to saturated, long fatty acyl chain Gb3 species in the outer membrane leaflet.
  • LecA binding induces dynamic PIP3 clusters in the inner membrane leaflet.
  • Flotillins and the GPI-anchored protein CD59 are integral to the LecA-interacting membrane domain.
  • Depletion of flotillins or CD59 reduced P. aeruginosa PAO1 invasiveness by approximately 50%.

Conclusions:

  • The LecA-Gb3 interaction initiates the formation of a specialized plasma membrane domain.
  • This domain is enriched in saturated Gb3, CD59, PIP3, and flotillins, facilitating P. aeruginosa uptake.
  • Targeting this host-pathogen interaction pathway offers a potential strategy against P. aeruginosa infections.
Keywords:
BacteriaEndocytosisGlycosphingolipidHost–pathogen interactionsLipid raftsSignaling

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