Pseudomonas aeruginosa quorum-sensing regulator RhlR (RhlR)

The Pseudomonas aeruginosa quorum-sensing regulator RhlR is a cytoplasmic transcription factor that functions as a central node in the complex quorum-sensing (QS) network of this opportunistic pathogen (UniProt: P54292). It is a member of the LuxR family and is specifically activated by the cognate autoinducer N-butyryl-L-homoserine lactone (C4-HSL), which is produced by the RhlI synthase (PubMed: 23602554). Once bound to its ligand, RhlR dimerizes and binds to specific DNA sequences, known as lux boxes, to trigger the expression of numerous genes involved in virulence, including those for pyocyanin, rhamnolipids, and various proteases (PubMed: 11544221). This system is crucial for the establishment of chronic infections and the formation of robust biofilms, particularly in the lungs of cystic fibrosis patients and in hospital-acquired infections (PubMed: 25103157). Because RhlR controls the production of factors that damage host tissues and suppress immune responses, it is a high-priority target for anti-virulence therapy. Small-molecule antagonists, such as thiolactones, are being investigated for their ability to disrupt RhlR signaling, potentially offering a way to treat multi-drug resistant P. aeruginosa by attenuating its pathogenicity rather than inhibiting growth (PubMed: 23602554).

Other names

Regulatory protein RhlRRhlR transcription factorC4-HSL receptorTranscriptional regulator RhlR

Antagonism of the RhlR receptor to prevent binding of the autoinducer C4-HSL, thereby inhibiting the transcription of virulence-associated genes and biofilm development (PubMed: 23602554).