Acyl-homoserine-lactone acylase (PvdQ) (PvdQ)

PvdQ is a periplasmic N-terminal nucleophile (Ntn) hydrolase from Pseudomonas aeruginosa that plays a dual role in bacterial physiology and pathogenesis [1, 5]. It is essential for the maturation of pyoverdine, the primary siderophore used by the bacterium to scavenge iron from the host environment, by removing a fatty acyl chain from the pyoverdine precursor [7, 17]. Additionally, PvdQ acts as a quorum-quenching enzyme by hydrolyzing long-chain N-acyl homoserine lactones (AHLs), which are signaling molecules that coordinate the expression of virulence factors and the formation of biofilms [2, 6]. Because PvdQ-deficient strains are unable to acquire iron effectively and exhibit significantly reduced virulence in infection models, the enzyme has become a prominent target for anti-virulence drug development [10, 15]. Small molecule inhibitors, such as the biaryl nitrile ML318 and boronic acid transition state analogues, have been shown to block PvdQ activity, thereby suppressing pyoverdine production and attenuating the pathogen's ability to cause disease [19, 20]. This pathoblocker approach aims to reduce the severity of infections, particularly in chronic conditions like cystic fibrosis, while minimizing the selective pressure for antibiotic resistance [8, 12].

Other names

PvdQ acylaseN-acyl-homoserine-lactone amidohydrolasePA2385AHL acylaseQuorum-quenching acylase

Inhibition of PvdQ enzymatic activity prevents the maturation of the siderophore pyoverdine and the degradation of quorum-sensing signaling molecules, leading to impaired iron acquisition and reduced expression of virulence factors.