Pseudomonas aeruginosa transcriptional activator protein LasR (LasR)

The Pseudomonas aeruginosa transcriptional activator protein LasR is a member of the LuxR family of transcription factors that acts as a receptor for the autoinducer N-3-oxo-dodecanoyl-l-homoserine lactone (3-oxo-C12-HSL). Upon ligand binding, LasR forms homodimers (multimers), translocates to DNA promoter regions, and activates expression of multiple genes involved in quorum-sensing, notably those controlling virulence factor production and biofilm formation[1][2][3][4]. LasR structure consists of a ligand-binding domain and a DNA-binding domain, forming a symmetrical dimer upon autoinducer binding[3][4]. Clinically, loss-of-function mutations in LasR are common in persistent P. aeruginosa infections such as those seen in cystic fibrosis patients and are associated with altered fitness under low-oxygen conditions and changes in bacterial metabolism[5]. LasR is actively pursued as a therapeutic target for bacterial virulence attenuation, mainly through the design of small-molecule inhibitors and synthetic quorum-sensing modulators[3][4][6]. However, no drugs are currently approved for clinical use against LasR, and significant challenges exist, such as resistance development and interaction redundancy in bacterial communication networks.

Other names

LasR proteinlasR gene productQuorum-sensing regulator LasRLuxR family transcriptional activatorPA1430 (Pseudomonas aeruginosa locus)

Competitive inhibition of autoinducer binding (e.g., synthetic antagonists block 3-oxo-C12-HSL binding); Allosteric modulation altering ligand specificity or potency; Stabilization or destabilization of active multimeric conformation