LasR quorum-sensing regulator (LasR)

LasR is a transcriptional activator and a central component of the quorum-sensing (QS) signaling network in the opportunistic human pathogen Pseudomonas aeruginosa [1, 3]. It belongs to the LuxR family of proteins and functions as a cytoplasmic receptor that responds to the autoinducer signal N-3-oxododecanoyl-L-homoserine lactone (3-oxo-C12-HSL) [1, 2]. Upon ligand binding, LasR undergoes a conformational change and homodimerizes, allowing it to bind to specific DNA promoter regions known as 'las boxes' to initiate the transcription of genes encoding various virulence factors, including elastases, alkaline protease, and exotoxin A [3, 4]. This regulatory hierarchy places LasR at the apex of the P. aeruginosa QS system, where it also triggers the expression of downstream regulators like RhlR and PqsR, thereby coordinating biofilm formation and host colonization [2, 5]. Given its pivotal role in pathogenicity, LasR is a major target for anti-virulence drug development, with various small-molecule inhibitors being explored to attenuate bacterial virulence without inducing the strong selective pressure associated with traditional bactericidal antibiotics [4, 6]. Sources: [1] UniProt Consortium. UniProtKB - P25084 (LASR_PSEAE). [2] Moradali, M. F., et al. (2017). Pseudomonas aeruginosa Lifestyle: A User's Guide to Pathogenesis. Emerging Microbes & Infections. [3] Bottomley, A. L., et al. (2007). Molecular insights into Quorum Sensing in Pseudomonas aeruginosa from the crystal structure of LasR. Journal of Biological Chemistry. [4] O'Loughlin, C. T., et al. (2013). A quorum-sensing inhibitor blocks Pseudomonas aeruginosa virulence and biofilm formation. PNAS. [5] Papenfort, K., & Bassler, B. L. (2016). Quorum sensing signal-response systems in Gram-negative bacteria. Nature Reviews Microbiology. [6] Paczkowski, J. E., et al. (2017). Flavonoids as Quorum Sensing Inhibitors. Molecules.

Other names

Transcriptional activator protein LasRLasR proteinLuxR-type transcriptional regulator LasR

Competitive antagonism of the autoinducer binding site, leading to inhibition of LasR dimerization and subsequent transcriptional activation of virulence genes.