Regulatory protein RhlR (RhlR)

Regulatory protein RhlR is a central transcription factor within the complex quorum-sensing (QS) hierarchy of Pseudomonas aeruginosa, a major cause of hospital-acquired infections [UniProt: P54292]. It is primarily activated by the signaling molecule N-butyryl-L-homoserine lactone (C4-HSL), which is produced by the synthase RhlI. Upon activation, RhlR binds to specific DNA sequences to trigger the expression of genes involved in the production of secondary metabolites and virulence factors, such as rhamnolipids, pyocyanin, and elastase [PubMed: 25646000]. These factors are essential for the bacterium's ability to form robust biofilms and evade the host immune system, particularly in the lungs of cystic fibrosis patients [PubMed: 30104361]. Because RhlR controls virulence rather than essential growth processes, it is considered a high-priority target for anti-virulence therapies that aim to disarm the pathogen without exerting the strong selective pressure associated with traditional antibiotics [PubMed: 28846096]. Experimental inhibitors, including synthetic AHL analogs and natural products like baicalein, have demonstrated the potential to reduce P. aeruginosa pathogenicity by disrupting RhlR-mediated signaling [PubMed: 31263131].

Other names

RhlRTranscriptional regulator RhlRQuorum-sensing regulator RhlRLuxR-type transcriptional regulator RhlR

Antagonism of the RhlR transcription factor by competing with the autoinducer N-butyryl-L-homoserine lactone (C4-HSL) or disrupting RhlR-DNA binding, thereby inhibiting the expression of virulence-associated genes.