The structure-function relationship of Pseudomonas aeruginosa in infections and its influence on the microenvironment

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. We review microbe-microbe and host-microbe interactions and their influence on the bacterial microenvironment alongside alternative interventions based on the physiology of P. aeruginosa in infections, where the bacteria are often found as small aggregates embedded in host material and surrounded by immune cells.

Automated summary

Pseudomonas aeruginosa establishes a microenvironmental niche in chronic infections, adapting to host responses by slowing down metabolism and exhibiting distinct adaptive traits. Understanding the microenvironmental ecology of P. aeruginosa in chronic infections is crucial for combating persistent bacterial infections.