Transcriptional activator LasR (LasR)

Transcriptional activator LasR is a pivotal component of the quorum sensing (QS) hierarchy in the Gram-negative bacterium Pseudomonas aeruginosa (UniProt P06271). It functions as a transcription factor that is activated upon binding its cognate signal molecule, N-3-oxo-dodecanoyl-L-homoserine lactone (3-oxo-C12-HSL) (Pearson et al., 1994, PNAS). Once activated, LasR dimerizes and binds to specific 'las boxes' in promoter regions, triggering the expression of hundreds of genes associated with virulence, including elastases (lasB), proteases, and exotoxins, as well as genes critical for biofilm maturation and the activation of downstream QS systems like Rhl and PQS (Schuster et al., 2003, J. Bacteriol). In clinical settings, LasR-mediated virulence is central to the pathogenesis of chronic infections in cystic fibrosis and immunocompromised patients (Hoffman et al., 2009, Lancet Infect Dis). Because LasR controls virulence rather than essential growth, it is a high-priority target for 'anti-virulence' therapeutic strategies, which aim to attenuate infection without exerting the same selective pressure for resistance as traditional antibiotics (Hentzer et al., 2003, EMBO J). Various synthetic and natural compounds, such as baicalein and N-acyl homoserine lactone (AHL) analogs, have been developed to inhibit LasR by competing for the ligand-binding site or disrupting the protein's folding and stability (O’Loughlin et al., 2013, PNAS).

Other names

LuxR-type transcriptional regulator LasRN-acyl-homoserine lactone-dependent transcriptional regulator LasRAcyl-homoserine lactone receptor

Competitive inhibition of the autoinducer (3-oxo-C12-HSL) binding site; disruption of protein dimerization; induction of LasR protein misfolding or accelerated degradation