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Updated: Nov 26, 2025
Long Term Chronic Pseudomonas aeruginosa Airway Infection in Mice
Published on: March 17, 2014
Airway immunometabolites fuel Pseudomonas aeruginosa infection
Sebastián A Riquelme1, Alice Prince2
1Department of Pediatrics, Columbia University, New York, NY, 10032, USA.
Abstract:
Pulmonary infections are associated with a brisk inflammatory reaction to bacterial surface components. Lipopolysaccharides (LPS) trigger macrophage activation and release of mitochondrial metabolites that control the intensity of the immune response. Whereas succinate induces oxidative stress (ROS), HIF1α stabilization, glycolysis and IL-1β release, itaconate suppresses inflammation by inhibiting succinate oxidation, glycolytic flux and promoting anti-oxidant Nrf2-HO-1 functions. P. aeruginosa is a major pathogen associated with acute and chronic lung infection. Although both secreted toxins, LPS and proteases are key factors to establish acute P. aeruginosa pneumonia, lack of these components in chronic P. aeruginosa isolates suggest these organisms exploit other mechanisms to adapt and persist in the lung. Upon inhalation, P. aeruginosa strains trigger airway macrophage reprograming and bacterial variants obtained from acutely and chronically infected subjects exhibit metabolic adaptation consistent with succinate and itaconate assimilation; namely, high expression of extracellular polysaccharides (EPS), reduced lptD-LPS function, increased glyoxylate shunt (GS) activity and substantial biofilm production. In this review we discuss recent findings illustrating how P. aeruginosa induces and adapts to macrophage metabolites in the human lung, and that catabolism of succinate and itaconate contribute to their formidable abilities to tolerate oxidative stress, phagocytosis and immune clearance.
Insights
Pseudomonas aeruginosa adapts to lung infections by altering its metabolism, utilizing macrophage-derived succinate and itaconate. This metabolic reprogramming enhances bacterial survival against oxidative stress and immune defenses.
Area of Science:
- Immunology
- Microbiology
- Metabolic pathways
Background:
- Pulmonary infections trigger inflammatory responses mediated by macrophage activation and mitochondrial metabolites.
- Succinate and itaconate are key metabolites influencing immune responses, with succinate promoting inflammation and itaconate suppressing it.
- Pseudomonas aeruginosa (P. aeruginosa) is a significant cause of lung infections, employing various mechanisms to establish infection.
Purpose of the Study:
- To review recent findings on how P. aeruginosa interacts with and adapts to macrophage metabolites in the human lung.
- To elucidate the role of succinate and itaconate catabolism in P. aeruginosa's persistence and immune evasion strategies.
Main Methods:
- Review of current literature on P. aeruginosa pathogenesis and host-pathogen interactions.
- Analysis of metabolic adaptations in P. aeruginosa strains from acute and chronic lung infections.
- Discussion of bacterial mechanisms like extracellular polysaccharide (EPS) production, altered lipopolysaccharide (LPS) function, and glyoxylate shunt (GS) activity.
Main Results:
- P. aeruginosa strains from infected subjects show metabolic adaptation, assimilating succinate and itaconate.
- Chronic P. aeruginosa isolates exhibit mechanisms like high EPS expression, reduced LPS function, and increased GS activity.
- Bacterial catabolism of succinate and itaconate contributes to P. aeruginosa's resistance to oxidative stress and phagocytosis.
Conclusions:
- P. aeruginosa actively reprograms airway macrophages and adapts its metabolism to utilize host-derived metabolites.
- Metabolic assimilation of succinate and itaconate is crucial for P. aeruginosa's ability to persist in the lung and evade immune clearance.
- Understanding these metabolic adaptations offers insights into P. aeruginosa pathogenesis and potential therapeutic targets.
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