January 9, 2020 –Research published in the journal Science by Ludwig Oxford’s Pedro Moura Alves and Max Planck’s Stefan Kaufmann gives new insight into the body’s monitoring of bacterial infections.
During an infection, bacteria such as Pseudomonas aeruginosa use a cell-to-cell signalling system called quorum sensing to communicate and coordinate their collective behavior. Quorum sensing is mediated by diffusible chemicals released by bacteria and is essential to efficient bacterial colonization and infection. Disrupting quorum sensing is seen as an attractive new strategy to combat the growing problem of antibiotic resistance, a critical challenge to global health.
Researchers have known for some time that the body can sense the chemical signals transmitted by bacteria and use the information to modulate its responses to infection (not all bacterial incursions rise to a level that poses a threat). What was less clear was how precisely that eavesdropping occurs. Pedro Moura Alves has previously shown that the Aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor that influences the immune response, can bind bacterial phenazines, which are downstream mediators of quorum signalling (Nature 2014). In their latest publication in Science, Pedro Moura Alves, Stefan Kaufmann (Max Planck Institute for Infection Biology, Berlin) and their colleagues show that AhR can also detect a variety of other quorum sensing molecules. AhR’s versatility allows the body to respond appropriately to the stage of bacterial infection, and not waste energy marshalling an immune response if bacterial levels are below a potentially dangerous threshold. Further, with a greater understanding of the AhR-quorum sensing cross-talk, this pathway could be exploited as a new host-directed therapeutic strategy against P. aeruginosa, a notable pathogen in cystic fibrosis patients and the immune-compromised.