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The Pseudomonas quinolone signal-iron(III) complex (PQS-Fe3+) is a specialized molecular assembly formed by the Pseudomonas quinolone signal (PQS; 2-heptyl-3-hydroxy-4-quinolone) and ferric iron. In Pseudomonas aeruginosa, PQS serves a dual role as both a quorum-sensing signaling molecule and a siderophore-like agent that chelates iron from the environment (Diggle et al., 2007). The formation of the PQS-Fe3+ complex is vital for the auto-induction of the PQS system and the subsequent regulation of virulence factors such as pyocyanin, rhamnolipids, and various proteases (Bredenbruch et al., 2006). This complex is particularly significant in chronic infections, such as those found in the lungs of cystic fibrosis patients, where iron is a limiting nutrient and bacterial coordination is essential for biofilm maintenance (Rampioni et al., 2016). Therapeutic interventions targeting this complex often involve the use of gallium, which acts as a redox-inactive iron mimic that replaces iron in the complex to disrupt bacterial metabolism (Bonchi et al., 2014). Other strategies include small molecules designed to inhibit the PQS receptor (PqsR/MvfR) or the enzymes involved in PQS biosynthesis, thereby preventing the formation or recognition of the signaling complex. By disrupting the PQS-Fe3+ signaling axis, these treatments aim to reduce bacterial virulence and enhance the efficacy of conventional antibiotics.
Quorum sensing inhibition and iron metabolism disruption
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