Recent Advances in the Discovery of PqsD Inhibitors as Antimicrobial Agents.

The treatment of the infections caused by Pseudomonas aeruginosa, an opportunistic Gram-negative bacterium, is very difficult. High intrinsic tolerance toward common antibiotics and the development of new resistant strains challenge us to find a new treatment as soon as possible. PqsD is an enzyme essential for the P. aeruginosa quorum-sensing apparatus, which catalyzes the final and key step in the biosynthesis of 4-hydroxy-2-heptylquinolone (HHQ), which is a signal molecule of the P. aeruginosa quorum-sensing system. In this review, following an outline on their structures, we present a brief introduction of the PqsD inhibitors including their mechanisms of action, inhibitory activity, and structure-activity relationships.