Campylobacter jejuni lipooligosaccharide sialylation, phosphorylation, and amide/ester linkage modifications

Holly N Stephenson1, Constance M John, Neveda Naz

  • 1Infectious Diseases and Microbiology Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, United Kingdom.

Insights

Campylobacter jejuni lipooligosaccharide (LOS) structure variations significantly impact Toll-like receptor 4 (TLR4) activation. Specific structural changes in LOS correlate with immune cell responses and bacterial source, particularly in livestock-associated strains.

Area of Science:

  • Microbiology
  • Immunology
  • Structural Biology

Background:

  • Campylobacter jejuni is a primary cause of bacterial gastroenteritis.
  • C. jejuni lipooligosaccharide (LOS) activates innate immunity via Toll-like receptor 4 (TLR4).
  • Previous studies identified structural variations in C. jejuni LOS, including the oligosaccharide (OS) and lipid A (LA) moieties.

Purpose of the Study:

  • To investigate LOS structural variations in C. jejuni strains from diverse ecological sources.
  • To analyze the impact of these structural variations on TLR4 activation.
  • To correlate LOS structure with bacterial ecological origin.

Main Methods:

  • MALDI-TOF MS was used to characterize LOS structural variations in 15 C. jejuni isolates.
  • Cytokine induction was measured in THP-1 cells and primary human monocytes.
  • LOS structural features were correlated with TLR4 activation levels and bacterial source.

Main Results:

  • Structural variations in OS sialylation, LA composition, and phosphorylation correlated with TLR4 activation.
  • LOS-induced inflammatory responses mimicked those of live C. jejuni bacteria.
  • OS sialylation, but not LA structure, was associated with livestock-associated C. jejuni strains.

Conclusions:

  • Variations in C. jejuni LOS structure, specifically OS sialylation, LA, and phosphorylation, modulate TLR4 activation and subsequent immune responses.
  • LOS is a key bacterial component driving host immunity during C. jejuni infection.
  • Ecological source influences C. jejuni LOS structure, with implications for host-pathogen interactions.

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