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Updated: Sep 11, 2025
Long Term Chronic Pseudomonas aeruginosa Airway Infection in Mice
Published on: March 17, 2014
A chronic Acinetobacter baumannii pneumonia model to study long-term virulence factors, antibiotic treatments, and
Clay D Jackson-Litteken1,2, Gisela Di Venanzio1, Manon Janet-Maitre1
1Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO, USA.
Abstract:
Acinetobacter baumannii causes prolonged infections that disproportionately affect immunocompromised populations. Our understanding of A. baumannii respiratory pathogenesis relies on an acute murine infection model with limited clinical relevance that employs an unnaturally high number of bacteria and requires assessment of bacterial load at 24-36 h post-infection. Here, we demonstrate that low intranasal inoculums in tlr4 mutant mice allows for infections lasting at least 3 weeks. Using this "chronic infection model" we determine the adhesin InvL is a virulence factor required during later stages of infection, despite being dispensable in the early phase. We also demonstrate that the chronic model enables distinction between antibiotics that, although initially reduce bacterial burden, either lead to clearance or result in the formation of potential bacterial persisters. To illustrate how our model can be applied to study polymicrobial infections, we inoculate mice with an active A. baumannii infection with Staphylococcus aureus or Klebsiella pneumoniae. We find that S. aureus exacerbates infection, while K. pneumoniae enhances A. baumannii clearance. In all, the chronic model overcomes some limitations of the acute pulmonary model, expanding our capabilities to study A. baumannii pathogenesis and lays the groundwork for the development of similar models for other opportunistic pathogens.
Insights
Researchers developed a new chronic mouse model for Acinetobacter baumannii infections. This model better reflects real-world infections, revealing new insights into virulence factors and antibiotic effectiveness.
Area of Science:
- Microbiology
- Infectious Diseases
- Immunology
Background:
- Acinetobacter baumannii causes severe, prolonged infections, particularly in immunocompromised individuals.
- Existing acute murine models have limitations in clinical relevance due to high bacterial loads and short observation periods.
Purpose of the Study:
- To develop a more clinically relevant chronic infection model for Acinetobacter baumannii.
- To investigate the role of the adhesin InvL in later stages of infection.
- To evaluate antibiotic efficacy and polymicrobial interactions in a chronic infection setting.
Main Methods:
- Establishment of a chronic Acinetobacter baumannii infection model in tlr4 mutant mice using low intranasal inoculums.
- Assessment of bacterial load and virulence factor roles over a 3-week infection period.
- Inoculation with polymicrobial pathogens (Staphylococcus aureus, Klebsiella pneumoniae) to study interactions.
Main Results:
- The chronic model supports infections lasting at least 3 weeks, offering a longer observation window.
- The adhesin InvL was identified as crucial for later-stage infection, but not early-stage.
- The model differentiated antibiotics based on their ability to achieve clearance versus persistence.
- Co-infection studies showed Staphylococcus aureus exacerbates infection, while Klebsiella pneumoniae aids Acinetobacter baumannii clearance.
Conclusions:
- The developed chronic infection model overcomes limitations of acute models, providing a valuable tool for studying Acinetobacter baumannii pathogenesis.
- This model enhances our understanding of virulence factors, antibiotic effects, and polymicrobial dynamics.
- It lays the foundation for similar chronic models for other opportunistic pathogens.
