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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.
Abstract:
Improved antimicrobial therapies against the classical spectrum of pathogenic bacteria which colonise the lungs of cystic fibrosis (CF) patients has resulted in improved life expectancy and quality of life. Bacterial species that are resistant to a broad range of antibiotics including Stenotrophomonas maltophilia and Alcaligenes xylosoxidans have now emerged as potential new pathogens to fill the niche. At present, it is unclear from clinical data whether these microbes are commensal or pathogenic. In this study we have quantified the inflammatory potential of lipopolysaccharide (LPS) from eight species of Gram-negative organisms which have been cultured with increasing frequency from CF patients. Inflammatory responses induced by LPS from whole human blood and a human-derived monocyte cell line (THP-1) were assessed. Enzyme-linked immunosorbent assays were used to detect interleukin-6, interleukin-8, and tumour necrosis factor alpha (TNF). A bioassay was also used to assess TNF activity. With the exception of S. maltophilia, LPS extracted from all of the bacteria tested upregulated, by varying degrees, expression of each of the proinflammatory cytokines assayed. This study represents the first comprehensive report of the endotoxic potential of a new wave of microbes which are associated with CF.
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.