Cyclodextrin inclusion in synthetic AHLs: advances in drug delivery and quorum sensing quenching

Many bacteria, such as Pseudomonas aeruginosa, regulate phenotypic transformation in a population density dependent manner through a phenomenon called quorum sensing (QS). For gram negative bacteria, QS depends on the synthesis, transmission and sensing of low molecular weight signal molecules, which are mainly n-acyl-l-homoserine lactones (AHLs). Efforts to destroy AHL mediated QS mainly focus on the development of synthetic AHL analogues (sahla), whose structure is similar to that of natural AHL [1]. However, like AHLs, these molecules tend to be hydrophobic and difficult to dissolve in water. Cyclodextrin (CDS) encapsulated AHL, which also proved the anti AHL mediated QS effect. Here, the affinity of sahlas and its hydrolysates for β - cyclodextrin inclusion complex was confirmed by fluorescence, nuclear magnetic resonance and mass spectrometry. In the study of host infection of Caenorhabditis elegans, these complexes inhibited the virulence of wild-type Pseudomonas aeruginosa for the first time. However, as CDs alone show anti QS effect, the application of CDs as a sahla carrier is a combination therapy, if not synergistic, it will also produce additional effects, which is shown by the survival ability model of Caenorhabditis elegans.