Fig. 2.

Mechanism of action of natural versus artificial antimicrobial compounds targeting riboswitches. Left panel: In most of the cases riboswitches are involved in the regulatory feedback loops by sensing the concentration of the metabolite (pink diamond) produced or imported into the cell by proteins under their control. When the concentration of the compound is dropping due to use in cell metabolism, the protein expression is activated (ON). After rise of the metabolite concentration, expression is again suppressed (OFF). Right panel: The riboswitches are targeted by artificial analogs of the original ligands (turquoise diamond). In order to be effective, the analog should not be used as a substrate in cell metabolism, causing permanent stalling of the riboswitch in the bound state. In case of the perturbation of a typical feedback loop, such stalling will lead to inhibition of the metabolite synthesis or uptake leading to cell death