Endotoxic activity of lipopolysaccharides isolated from emergent potential cystic fibrosis pathogens

M L Hutchison1, E C Bonell, I R Poxton

  • 1Department of Medical Microbiology, University of Edinburgh Medical School, Teviot Place, Edinburgh, UK.

Insights

New Gram-negative bacteria like Stenotrophomonas maltophilia are colonizing cystic fibrosis (CF) lungs. Their lipopolysaccharide (LPS) triggers significant inflammatory responses, indicating pathogenic potential in CF patients.

Area of Science:

  • Microbiology and Immunology
  • Cystic Fibrosis Research
  • Bacterial Pathogenesis

Background:

  • Advances in antimicrobial therapies have improved outcomes for cystic fibrosis (CF) patients.
  • Antibiotic-resistant bacteria, including Stenotrophomonas maltophilia and Alcaligenes xylosoxidans, are increasingly prevalent in CF airways.
  • The pathogenic role of these emerging bacteria in CF remains unclear.

Purpose of the Study:

  • To quantify the inflammatory potential of lipopolysaccharide (LPS) from eight Gram-negative bacterial species frequently cultured from CF patients.
  • To assess the endotoxic capacity of these emerging CF-associated microbes.

Main Methods:

  • Lipopolysaccharide (LPS) was extracted from eight Gram-negative bacterial species.
  • Inflammatory responses were measured in whole human blood and THP-1 monocyte cell line.
  • Quantification of pro-inflammatory cytokines (interleukin-6, interleukin-8, tumor necrosis factor alpha) using ELISA and TNF bioassay.

Main Results:

  • LPS from all tested bacteria, except S. maltophilia, significantly upregulated pro-inflammatory cytokine expression.
  • Varying degrees of inflammatory response were observed across different bacterial LPS.
  • TNF activity was also assessed via bioassay.

Conclusions:

  • This study provides the first comprehensive assessment of the endotoxic potential of emerging bacteria in CF.
  • The findings suggest that LPS from these newly prevalent bacteria can induce significant inflammatory responses.
  • This highlights their potential pathogenic role in cystic fibrosis lung infections.

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