Resistance Is Not Futile: The Role of Quorum Sensing Plasticity in Pseudomonas aeruginosa Infections and Its Link to Intrinsic Mechanisms of Antibiotic Resistance

Abstract

Bacteria use a cell-cell communication process called quorum sensing (QS) to orchestrate collective behaviors. QS relies on the group-wide detection of extracellular signal molecules called autoinducers (AI). Quorum sensing is required for virulence and biofilm formation in the human pathogen Pseudomonas aeruginosa. In P. aeruginosa, LasR and RhlR are homologous LuxR-type soluble transcription factor receptors that bind their cognate AIs and activate the expression of genes encoding functions required for virulence and biofilm formation. While some bacterial signal transduction pathways follow a linear circuit, as phosphoryl groups are passed from one carrier protein to another ultimately resulting in up- or down-regulation of target genes, the QS system in P. aeruginosa is a dense network of receptors and regulators with interconnecting regulatory systems and outputs. Once activated, it is not understood how LasR and RhlR establish their signaling hierarchy, nor is it clear how these pathway connections are regulated, resulting in chronic infection. Here, we reviewed the mechanisms of QS progression as it relates to bacterial pathogenesis and antimicrobial resistance and tolerance.

Comparative Proteomic Analysis of Protein Patterns of Stenotrophomonas maltophilia in Biofilm and Planktonic Lifestyles

“…The signal reaching a threshold concentration is perceived by a sensor system that activates the QS [ 17 ]. The most frequently produced signals from Proteobacteria have been grouped in the class of N-acyl homoserine lactones (N-AHSLs), almost always synthesized through a LuxI-like synthase and perceived through a sensor-regulator system LuxR-like [ 18 ]. In S. maltophilia , the main QS system relies on the Diffusible Signal Factor (DSF) cis-11-methyl-2-dodecenoic acid, which modulates motility, biofilm formation, antibiotic resistance, and virulence [ 19 ].…”

Multi‐focused laboratory experiments based on Quorum Sensing and Quorum Quenching for acquiring Microbial Physiology concepts

“…Among other, several genes coding for extracellular proteases are activated by QS in P. aeruginosa PAO1. LasA protease and LasB elastase are the best characterized and the ones that give the name to the LasI-LasR QS system (Simanek and Paczkowski 2022;Schuster et al 2003). Thought both Las and Rhl QS systems upregulate the expression of the corresponding lasA and lasB coding genes, the former is more prevalent than the latter.…”

Resistance, Tolerance, Virulence and Bacterial Pathogen Fitness—Current State and Envisioned Solutions for the Near Future

“…Recent studies concerning the biofilm-forming bacteria suggested the associative effect over the mechanisms of AR of both inflammatory endotoxins/LPS (with intense action in a biofilm formed on tissues) and the expression of the stress genes [ 120 , 121 ]. According to some authors, the QS mechanism and signal molecules are associated with biofilm formation and intrinsic resistance mechanisms in P. aeruginosa , but even environmental factors play a major role in the activation of virulence genes [ 122 ].…”