Quorum Sensing Modulation in Gram-Negative Bacteria

Quorum sensing (QS) is a density-dependent regulatory mechanism by which Gram-negative bacteria synchronise communal behaviours through the production, release and detection of small diffusible signals known as autoinducers. Predominantly based on N-acyl homoserine lactones (AHLs), this communication network controls a wide range of phenotypes including biofilm formation, secretion of virulence factors, motility and antibiotic tolerance. Modulation of QS offers a promising anti-virulence strategy: by intercepting or degrading signals, antagonising receptors or deploying signal analogues, it is possible to disarm pathogenic populations without exerting the selective pressure associated with conventional antimicrobials. Such approaches hold global significance for addressing antimicrobial resistance, for enhancing crop protection in agriculture, for preventing biofouling in industrial settings and for manipulating beneficial microbiomes. Recent advances have elucidated the structural basis of receptor–ligand interactions, uncovered interconnections between QS and other second-messenger networks, and revealed opportunities for rational design of inhibitors or enzymatic quenchers to control bacterial behaviour in diverse environments.

Research from Nature Portfolio

Recent studies have uncovered the dual functionality of fungal-derived metabolites in controlling QS and cyclic di-GMP signalling. One investigation demonstrated that terrein, isolated from a marine Aspergillus species, effectively antagonises multiple LuxR-type receptors in Pseudomonas aeruginosa, leading to marked decreases in elastase, pyocyanin and rhamnolipid production as well as impaired biofilm formation. Importantly, terrein also reduced intracellular levels of the second messenger c-di-GMP by inhibiting a diguanylate cyclase, thereby linking QS inhibition to dispersal of established biofilms. This work provides a structural and biochemical framework for the design of multifunctional anti-virulence agents targeting both signalling pathways to combat persistent infections.

Quorum Sensing Modulation in Gram-Negative Bacteria publication trend

The graph below shows the total number of articles in quorum sensing modulation in gram-negative bacteria across all publications each year (not limited to Nature Index journals).

Technical terms

Autoinducer: Small signalling molecule secreted by bacteria whose concentration reflects population density and regulates gene expression.

Acyl-homoserine lactone (AHL): A class of autoinducers commonly used by Gram-negative bacteria to mediate quorum sensing.

LuxR-type receptor: Transcriptional regulator that binds AHLs to activate or repress QS-controlled genes.

Cyclic di-GMP (c-di-GMP): Intracellular second messenger that influences biofilm formation, motility and cell cycle progression.

Quorum sensing inhibitor (QSI): Compound or enzyme that interferes with signal production, detection or transduction in QS pathways.

References

1. Terrein is an inhibitor of quorum sensing and c-di-GMP in Pseudomonas aeruginosa: a connection between quorum sensing and c-di-GMP. Scientific Reports (2018).
2. Norlobaridone Inhibits Quorum Sensing-Dependent Biofilm Formation and Some Virulence Factors in Pseudomonas aeruginosa by Disrupting Its Transcriptional Activator Protein LasR Dimerization. Biomolecules (2023).
3. In silico anti-quorum sensing activities of phytocompounds of Psidiumguajava in Salmonellaenterica serovar Typhi. Journal of Umm Al-Qura University for Applied Sciences (2023).
4. Quorum Sensing Signal Selectivity and the Potential for Interspecies Cross Talk. mBio (2019).