Lipopolysaccharide structure impacts the entry kinetics of bacterial outer membrane vesicles into host cells

Eloise O'Donoghue, Natalie Sirisaengtaksin, Douglas Browning, Ewa Bielska, Mohammed Hadis, Francisco Fernandez-Trillo, Luke Alderwick, Sara Jabbari, Anne Marie Krachler

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)
239 Downloads (Pure)

Abstract

Outer membrane vesicles are nano-sized microvesicles shed from the outer membrane of Gram-negative bacteria and play important roles in immune priming and disease pathogenesis. However, our current mechanistic understanding of vesicle - host cell interactions is limited by a lack of methods to study the rapid kinetics of vesicle entry and cargo delivery to host cells. Here, we describe a highly sensitive method to study the kinetics of vesicle entry into host cells in real-time using a genetically encoded, vesicle-targeted probe. We found that the route of vesicular uptake, and thus entry kinetics and efficiency, are shaped by bacterial cell wall composition. The presence of lipopolysaccharide O antigen enables vesicles to bypass clathrin-mediated endocytosis, which enhances both their entry rate and efficiency into host cells. Collectively, our findings highlight the composition of the bacterial cell wall as a major determinant of secretion-independent delivery of virulence factors during Gram-negative infections.
Original languageEnglish
Pages (from-to)e1006760
JournalPLoS pathogens
Volume13
Issue number11
DOIs
Publication statusPublished - 29 Nov 2017

Keywords

  • outer membrane vesicles
  • lipopolysaccharide
  • serotype
  • FRET kinetics
  • extracellular vesicles
  • cargo uptake
  • vesicle trafficking
  • endocytosis

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