β-Cyclodextrin encapsulation of synthetic AHLs: drug delivery implications and quorum-quenching exploits

Posted by

Many bacteria, such as Pseudomonas aeruginosa, regulate phenotypic switching in a population density-dependent manner through a phenomenon known as quorum sensing (QS). For Gram-negative bacteria, QS relies on the synthesis, transmission, and perception of low molecular weight signal molecules that are predominantly N-acyl-L-homoserine lactones (AHLs). Efforts to disrupt AHL-mediated QS have largely focused on the development of synthetic AHL analogues (SAHLAs) that are structurally similar to native AHLs [1]. However, like AHLs, these molecules tend to be hydrophobic and are poorly soluble under aqueous conditions. CDs encapsulate AHLs and have also demonstrated anti-AHL-mediated QS effects. Here, using fluorescence spectroscopy, nuclear magnetic resonance spectrometry, and mass spectrometry, the affinity of SAHLAs, as well as their hydrolysis products, for β-CD inclusion was confirmed. These complexes inhibited wildtype P. aeruginosa virulence in a Caenorhabditis elegans host infection study, for the first time. However, as CDs alone demonstrate anti-QS effects, the application of CDs as SAHLA delivery vehicles is a per se combination therapy that elicits additive, if not synergistic, effects that was shown here using a C. elegans viability model.

These efforts confirm the potential of β-CDs for the improved delivery of SAHLAs at the host:microbial interface, expanding the utility of this approach as a strategy for probing and controlling QS.

For the literature background of CD-mediated quorum sensing you can see: https://cyclolab.hu/userfiles/cdn_2017_jan.pdf



[1] Eric W Ziegler, Alan B Brown, Nasri Nesnas, Chris Chouinard, Anil K Mehta, Andrew George Palmer: β-Cyclodextrin encapsulation of synthetic AHLs: drug delivery implications and quorum-quenching exploits. Chembiochem. 2020 Nov 25. doi: 10.1002/cbic.202000773. Online ahead of print.

The featured image is from The biology notes (https://thebiologynotes.com/quorum-sensing-in-bacteria/)

One comment

Leave a Reply

This site uses Akismet to reduce spam. Learn how your comment data is processed.