Regulatory protein RhlR (RhlR) (RhlR)

Regulatory protein RhlR is a central transcriptional regulator within the complex quorum-sensing (QS) hierarchy of the opportunistic pathogen Pseudomonas aeruginosa (UniProt P54292). It functions as a LuxR-type receptor that is activated upon binding its cognate autoinducer, N-butyryl-L-homoserine lactone (C4-HSL), which is produced by the synthase RhlI (Mukherjee et al., 2017). Once activated, RhlR forms a dimer and binds to specific DNA sequences (lux boxes) to trigger the expression of genes involved in the production of secondary metabolites and virulence factors, such as rhamnolipids, pyocyanin, and elastase (O'Loughlin et al., 2013). These factors are essential for the bacteria's ability to form robust biofilms, evade the host immune system, and cause tissue damage during chronic infections, particularly in patients with cystic fibrosis or compromised immune systems (Eickhoff et al., 2021). Because RhlR controls virulence rather than essential growth processes, it is considered a high-priority target for anti-virulence therapy. Inhibiting RhlR aims to disarm the pathogen and enhance its clearance by the host immune system or conventional antibiotics, potentially reducing the selective pressure that leads to traditional antibiotic resistance (Mukherjee et al., 2017; Eickhoff et al., 2021).

Other names

Quorum-sensing transcriptional regulator RhlRRhlR regulatorTranscription factor RhlR

Competitive antagonism of the autoinducer binding site or disruption of the RhlR-DNA binding interface to inhibit the transcription of virulence-associated genes.