Posted by One of the most emerging multidrug-resistant strains is the Gram-negative, opportunistic pathogen Pseudomonas aeruginosa, whose resistance was qualified “critical” by the WHO Global Priority Pathogens List in 2017. The large arsenal of virulence factors, secondary metabolites, and the antibiotic resistance of the bacteria – as much as 6% of all genes – are controlled through a complex hierarchical system of four main quorum sensing (QS) routes and several chemically distinct classes of signal molecules. Quorum sensing is a communication mechanism by which bacterial cells interact with each other in a niche, species, or population. The QS occurs through the production, detection, and response to signal molecules (autoinducers) – low molecular weight compounds of diverse structure and origin.
These days, the spread of antibiotic-resistant bacterial strains and their infections in a broad spectrum of hosts requires innovative methods targeting bacterial virulence. The disruption of the QS in bacteria – quorum quenching (QQ) – opens new potential for efficiently overcoming this problem. The QS process can be distracted through various mechanisms, including obstructing the synthesis of the signal molecules, diminishing the activity of their receptors, breaking down or mimicking autoinducers, and preventing signals from binding to the receptors. The latter can be performed by molecular encapsulation using cyclodextrins (CDs). Cyclodextrins were demonstrated to efficiently modulate QS in several Gram-negative and Gram-positive model organisms – including Aliivibrio fischeri, Chromobacterium violaceum, and Serratia marcescens – by forming inclusion complexes with the signal molecules.
This research tested the effect of the native α- and β-cyclodextrin at various concentrations on the blue-colored pyocyanin pigment production of P. aeruginosa. The concentration- and time-dependent QQ effect of the native cyclodextrins and their widely used derivatives such as randomly methylated, quaternary amino and polymer derivatives, on fluorescent pyoverdine pigment production was also examined. The tested cyclodextrins significantly inhibited the production of both pigments, but the α- CDs to a greater extent. In the large-volume experimental system, 10 mM α-CD decreased the pyocyanin production by 58%, while β-CD only by ~40%. In the case of the pyoverdine (studied in a small-volume high-throughput system), the inhibitory effect of 12.5 mM native α-CD was 57%, while the inhibitory effect of the β-CDs was lower than 40%. The statistical analysis demonstrated the significant influence of the contact time and the CD concentration on the pyoverdine production of the bacteria.
Based on the result of this study, the potential of CDs as QQ agents and their role in an antivirulence strategy as molecular capsules for the signal molecules should be considered.
Ildikó Fekete‑Kertész, Zsófia Berkl, Kata Buda, Éva Fenyvesi, Lajos Szente, Mónika Molnár (2024) Quorum quenching effect of cyclodextrins on the pyocyanin and pyoverdine production of Pseudomonas aeruginosa. Applied Microbiology and Biotechnology 108, 271. https://doi.org/10.1007/s00253-024-13104-7