A lipid zipper triggers bacterial invasion

T. Eierhoff, B. Bastian, R. Thuenauer, J. Madl, A. Audfray, S. Aigal, S. Juillot, G.E. Rydell, S. Müller, S. de Bentzmann, A. Imberty, C. Fleck, W. Römer

Research output: Contribution to journalArticleAcademicpeer-review

53 Citations (Scopus)

Abstract

Glycosphingolipids are important structural constituents of cellular membranes. They are involved in the formation of nanodomains (“lipid rafts”), which serve as important signaling platforms. Invasive bacterial pathogens exploit these signaling domains to trigger actin polymerization for the bending of the plasma membrane and the engulfment of the bacterium—a key process in bacterial uptake. However, it is unknown whether glycosphingolipids directly take part in the membrane invagination process. Here, we demonstrate that a “lipid zipper,” which is formed by the interaction between the bacterial surface lectin LecA and its cellular receptor, the glycosphingolipid Gb3, triggers plasma membrane bending during host cell invasion of the bacterium Pseudomonas aeruginosa. In vitro experiments with Gb3-containing giant unilamellar vesicles revealed that LecA/Gb3-mediated lipid zippering was sufficient to achieve complete membrane engulfment of the bacterium. In addition, theoretical modeling elucidated that the adhesion energy of the LecA–Gb3 interaction is adequate to drive the engulfment process. In cellulo experiments demonstrated that inhibition of the LecA/Gb3 lipid zipper by either lecA knockout, Gb3 depletion, or application of soluble sugars that interfere with LecA binding to Gb3 significantly lowered P. aeruginosa uptake by host cells. Of note, membrane engulfment of P. aeruginosa occurred independently of actin polymerization, thus corroborating that lipid zippering alone is sufficient for this crucial first step of bacterial host-cell entry. Our study sheds new light on the impact of glycosphingolipids in the cellular invasion of bacterial pathogens and provides a mechanistic explication of the initial uptake processes.
Original languageEnglish
Pages (from-to)12895-12900
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number35
DOIs
Publication statusPublished - 2014

    Fingerprint

Keywords

  • pseudomonas-aeruginosa lectin
  • human endothelial-cells
  • epithelial-cells
  • host-cells
  • membrane invaginations
  • e-cadherin
  • pa-i
  • rafts
  • entry
  • receptor

Cite this

Eierhoff, T., Bastian, B., Thuenauer, R., Madl, J., Audfray, A., Aigal, S., ... Römer, W. (2014). A lipid zipper triggers bacterial invasion. Proceedings of the National Academy of Sciences of the United States of America, 111(35), 12895-12900. https://doi.org/10.1073/pnas.1402637111