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Updated: Jul 15, 2025
Long Term Chronic Pseudomonas aeruginosa Airway Infection in Mice
Published on: March 17, 2014
Ketogenesis promotes tolerance to Pseudomonas aeruginosa pulmonary infection
Kira L Tomlinson1, Ying-Tsun Chen1, Alex Junker1
1Department of Pediatrics, Columbia University, New York, NY 10032, USA.
Abstract:
Pseudomonas aeruginosa is a common cause of pulmonary infection. As a Gram-negative pathogen, it can initiate a brisk and highly destructive inflammatory response; however, most hosts become tolerant to the bacterial burden, developing chronic infection. Using a murine model of pneumonia, we demonstrate that this shift from inflammation to disease tolerance is promoted by ketogenesis. In response to pulmonary infection, ketone bodies are generated in the liver and circulate to the lungs where they impose selection for P. aeruginosa strains unable to display surface lipopolysaccharide (LPS). Such keto-adapted LPS strains fail to activate glycolysis and tissue-damaging cytokines and, instead, facilitate mitochondrial catabolism of fats and oxidative phosphorylation (OXPHOS), which maintains airway homeostasis. Within the lung, P. aeruginosa exploits the host immunometabolite itaconate to further stimulate ketogenesis. This environment enables host-P. aeruginosa coexistence, supporting both pathoadaptive changes in the bacteria and the maintenance of respiratory integrity via OXPHOS.
Insights
Ketogenesis promotes disease tolerance during Pseudomonas aeruginosa lung infections. This process involves ketone bodies shifting bacterial strains to reduce inflammation and maintain airway health via oxidative phosphorylation.
Area of Science:
- Immunology
- Microbiology
- Metabolism
Background:
- Pseudomonas aeruginosa is a Gram-negative pathogen causing destructive pulmonary inflammation.
- Chronic infection develops as hosts often become tolerant to bacterial burden.
Purpose of the Study:
- To investigate the role of ketogenesis in the host's shift from inflammation to disease tolerance during P. aeruginosa pneumonia.
Main Methods:
- Utilized a murine model of pneumonia.
- Analyzed the effects of ketone bodies and itaconate on P. aeruginosa and host lung tissue.
Main Results:
- Ketogenesis promotes a shift towards disease tolerance in P. aeruginosa lung infections.
- Ketone bodies select for P. aeruginosa strains with altered lipopolysaccharide (LPS) display.
- Keto-adapted strains reduce inflammatory cytokines and promote host oxidative phosphorylation (OXPHOS) for airway homeostasis.
- P. aeruginosa exploits itaconate to enhance host ketogenesis.
Conclusions:
- Ketogenesis is a key mechanism driving the transition from acute inflammation to chronic infection tolerance.
- This metabolic adaptation facilitates host-bacterial coexistence and preserves respiratory function through OXPHOS.
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