Resistance Is Not Futile: The Role of Quorum Sensing Plasticity in Pseudomonas aeruginosa Infections and Its Link to Intrinsic Mechanisms of Antibiotic Resistance

Bacteria use a cell-cell communication process called quorum sensing (QS) to orchestrate collective behaviors. QS relies on the group-wide detection of extracellular signal molecules called autoinducers (AI). Quorum sensing is required for virulence and biofilm formation in the human pathogen Pseudomonas aeruginosa. In P. aeruginosa, LasR and RhlR are homologous LuxR-type soluble transcription factor receptors that bind their cognate AIs and activate the expression of genes encoding functions required for virulence and biofilm formation. While some bacterial signal transduction pathways follow a linear circuit, as phosphoryl groups are passed from one carrier protein to another ultimately resulting in up- or down-regulation of target genes, the QS system in P. aeruginosa is a dense network of receptors and regulators with interconnecting regulatory systems and outputs. Once activated, it is not understood how LasR and RhlR establish their signaling hierarchy, nor is it clear how these pathway connections are regulated, resulting in chronic infection. Here, we reviewed the mechanisms of QS progression as it relates to bacterial pathogenesis and antimicrobial resistance and tolerance.

Automated summary

Bacteria use a process called quorum sensing to coordinate collective behaviors. This process relies on the detection of extracellular signal molecules known as autoinducers. In the human pathogen Pseudomonas aeruginosa, quorum sensing is important for virulence and biofilm formation. However, the signaling hierarchy and regulatory mechanisms of the receptors involved in this process are still not well understood, leading to chronic infection.