Quorum Sensing Roles in Pseudomonas aeruginosa Biofilm Formation: Intercellular Communication, Matrix Development, and Genetic Regulation

Abstract

Pseudomonas aeruginosa is a metabolically versatile opportunistic pathogen whose persistence in chronic infection is strongly associated with biofilm growth and coordinated population behavior. Biofilm development proceeds through reversible attachment, irreversible attachment, microcolony formation, three-dimensional maturation, and active dispersal. These stages are supported by an extracellular matrix composed principally of Psl, Pel, alginate, extracellular DNA, matrix-associated proteins, lipids, and outer membrane vesicles. Quorum sensing (QS) links population density and local chemical conditions to synchronized gene expression. The canonical network contains the LasI/LasR and RhlI/RhlR acyl-homoserine lactone systems and the PqsR-dependent alkyl-quinolone system, which use 3-oxo-C12-homoserine lactone, C4-homoserine lactone, HHQ, and the Pseudomonas quinolone signal as major autoinducers. Their cross-regulation controls matrix synthesis, rhamnolipid production, phenazines, extracellular enzymes, motility, extracellular DNA release, and biofilm architecture. QS is further integrated with cyclic di-GMP and Gac/Rsm signaling, while additional chemical communication systems involving IQS, cis-2-decenoic acid, polyamines, phenylacetic acid, and cyclic dipeptides may modulate behavior under particular environmental conditions. This review describes the stages and matrix biology of P. aeruginosa biofilms, explains how QS coordinates intercellular communication, and details the genes that connect signal synthesis and perception with biofilm formation. Future work should resolve the spatial and strain-dependent organization of these networks and evaluate multi-target quorum-quenching approaches in clinically realistic biofilm models.