Transcriptional activator protein LasR (LasR) (LasR)

Transcriptional activator protein LasR (LasR) is a LuxR-type regulator that serves as a master controller of the quorum-sensing (QS) system in the opportunistic pathogen Pseudomonas aeruginosa (UniProt: P25084). It is activated by the binding of its cognate autoinducer, N-3-oxo-dodecanoyl-L-homoserine lactone (3-oxo-C12-HSL), which promotes LasR dimerization and subsequent binding to lux-box sequences in the promoters of target genes (PubMed: 25105271). This regulatory cascade triggers the expression of numerous virulence factors, including elastases, pyocyanin, and exotoxin A, which are essential for host tissue degradation and immune evasion (PubMed: 30256134). Additionally, LasR is a critical factor in the formation and maintenance of bacterial biofilms, which contribute significantly to the chronic nature of infections and antibiotic resistance (PubMed: 16166553). As a therapeutic target, LasR is highly valued for anti-virulence strategies that aim to attenuate pathogenicity without imposing the strong selective pressure associated with traditional bactericidal antibiotics (PubMed: 29155350). Various small-molecule inhibitors, such as AHL analogs and non-native ligands like V-06-018, are currently being investigated for their ability to disrupt LasR-mediated signaling and enhance the clearance of multi-drug resistant P. aeruginosa (PubMed: 31430114). By disarming the bacteria rather than killing them, LasR inhibitors represent a promising approach to managing chronic infections in patients with cystic fibrosis or compromised immune systems.

Other names

LasR transcriptional regulatorQuorum-sensing control activator LasRLasR

Competitive antagonism of the autoinducer binding site, inhibition of protein dimerization, and prevention of DNA binding to target promoters.