LasR

LasR is a transcriptional regulator of the quorum-sensing system in Pseudomonas aeruginosa. It belongs to the LuxR family of transcription factors and acts as the central activator of the Las regulatory circuit, controlling numerous genes involved in virulence and community behavior.

LasR activity depends on binding of its autoinducer, 3-oxo-dodecanoyl-homoserine lactone (3OC12-HSL), produced by LasI. When cell density rises, 3OC12-HSL diffuses into the cell, binds LasR, and promotes dimerization and high-affinity binding to las box promoter sequences. This activates transcription of multiple targets, including lasI (positive feedback) and virulence-related genes such as lasB (elastase), lasA, toxA (exotoxin A), and enzymes associated with biofilm formation and host interaction.

LasR sits at the top of a hierarchical quorum-sensing network and cross-regulates other regulators, notably the RhlR/RhlI system and the PQS regulator PqsR, coordinating expression of the rhl and pqs regulons. Through these interactions, LasR influences a broad regulon that affects virulence factor production, surface attachment, motility, and metabolic adaptation.

Structure-wise, LasR comprises an N-terminal ligand-binding domain that recognizes 3OC12-HSL and a C-terminal DNA-binding domain containing a helix-turn-helix motif. Structural studies of the ligand-bound form have illuminated promoter recognition and dimerization essential for transcriptional activation.

Clinical and ecological relevance include its role in virulence and biofilm development in P. aeruginosa. In chronic infections, lasR-deficient mutants frequently arise, exhibiting altered metabolism and QS-independent traits that can affect pathogenicity and antibiotic tolerance. LasR remains a focal point in studies of quorum-sensing inhibitors as potential anti-virulence strategies.