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The structure-function relationship of Pseudomonas aeruginosa in infections and its influence on the microenvironment
Mads Lichtenberg1, Tim Holm Jakobsen1, Michael Kühl2
1Costerton Biofilm Center, Department of Immunology and Microbiology, University of Copenhagen, Blegdamsvej 3B, 2200, København, Denmark.
Abstract:
Pseudomonas aeruginosa is a human pathogen associated with both acute and chronic infections. While intensively studied, the basic mechanisms enabling the long-term survival of P. aeruginosa in the host, despite massive immune system attack and heavy antimicrobial treatment, remain to be identified. We argue that such infections may represent niche invasions by P. aeruginosa that influence the microenvironment by depleting host-derived substrate and activating the immune response. Bacteria embedded in cell aggregates establish a microenvironmental niche, where they endure the initial host response by slowing down their metabolism. This provides stable, lasting growth conditions with a constant, albeit slow supply of substrate and electron acceptors. Under such stable conditions, P. aeruginosa exhibits distinct adaptive traits, where its gene expression pattern reflects a life exposed to continuous attack by the host immune system and antimicrobials. Here, we review fundamental microenvironmental aspects of chronic P. aeruginosa infections and examine how their structural organization influences their in vivo microenvironment, which in turn affects the interaction of P. aeruginosa biofilm aggregates with the host immune system. We discuss how improving our knowledge about the microenvironmental ecology of P. aeruginosa in chronic infections can be used to combat persistent, hard-to-treat bacterial infections.
Insights
Chronic Pseudomonas aeruginosa infections persist by forming protective microenvironmental niches. These bacterial aggregates slow metabolism and adapt gene expression to survive host immune attacks and antimicrobial treatments, offering new therapeutic targets.
Area of Science:
- Microbiology
- Infectious Diseases
- Host-Pathogen Interactions
Background:
- Pseudomonas aeruginosa is a significant human pathogen causing acute and chronic infections.
- Mechanisms for long-term survival of P. aeruginosa against host defenses and antimicrobials are not fully understood.
- Chronic infections are often difficult to treat and eradicate.
Purpose of the Study:
- To review and understand the microenvironmental ecology of chronic P. aeruginosa infections.
- To examine how the structural organization of P. aeruginosa aggregates influences the in vivo microenvironment.
- To explore how microenvironmental factors affect host immune system interactions and bacterial survival.
Main Methods:
- Review of fundamental microenvironmental aspects of chronic P. aeruginosa infections.
- Examination of bacterial cell aggregate structural organization.
- Analysis of P. aeruginosa gene expression patterns under simulated host attack conditions.
Main Results:
- Chronic P. aeruginosa infections may represent niche invasions, altering the host microenvironment.
- Bacteria within cell aggregates establish a niche by slowing metabolism to endure host responses.
- Adaptive traits and altered gene expression reflect survival under continuous immune and antimicrobial pressure.
Conclusions:
- Understanding the microenvironmental ecology of P. aeruginosa is crucial for combating persistent infections.
- The structural organization of bacterial aggregates significantly impacts the in vivo microenvironment and host interaction.
- Targeting these microenvironmental niches could lead to novel strategies against hard-to-treat bacterial infections.
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