Visible-light-based modulation of bacterial quorum sensing with photoswitchable signal molecules

Controlling bacterial collective behaviour through manipulation of the quorum sensing (QS) system presents applicability for various ends, in both the inhibition and induction of these bacterial regulatory circuits using external signals. In addition to native functions, the repurposing of natural control elements for biotechnological applications has also garnered interest. Homoserine lactone (HSL) mediated QS has previously been coupled to light signals by photoswitchable signal molecule mimics; however, existing compounds have made use of UV-responsive azobenzenes, which may limit their use in biological settings. Here, we report two visible-light-responsive azobenzene-homoserine lactones (AB-HSL) that exhibit illumination-dependent induction activity in a bacterial reporter system. The employed electron donor-substitution balances red-shifting of the parent azobenzene moiety and the HSL-like motif of a 3-oxo-substituted lactone headgroup coupled to a nonpolar tail. The reported compounds provide a proof of concept for visible-light-based control of bacterial QS circuits and lay the groundwork for further development of photoresponsive signal molecules. Such systems may be adaptable in e.g. control of microbial consortia, spatiotemporal induction of specific bacterial behaviors, or modelling of natural QS systems.