Antibacterial lysine analogs that target lysine riboswitches

In Deiter's class today we talked about how riboswitches are good targets for small molecule inhibitors because they already endogenously bind to small molecules. In addition, because riboswitches often sense metabolites, the expression platform often contains genes that are essential to its survival. This then would make them good antibiotic targets. However, there are few examples of small molecule antibiotics that were designed to target riboswitches. Attached is one of those papers.
In this paper, Blount and co-workers target the bacterial lysine riboswitch which controls lysine biosynthesis. In most bacteria, the binding of lysine to the lysine riboswitch forms a transcription terminator, stopping the production of proteins that will produce more lysine and lysine intermediates. Therefore, finding an alternative small molecule that will bind to the lysine riboswitch, will halt lysine production and cause the bacteria to die. The way that this is done is by rational design, where the authors vary specific areas of the lysine side chain and determine dissociation constants by in-line probing. Below shows (a) the optical density of cultures grown in the presence of the analogs over time (b) this data was then plotted in a bar chart (c) shows the mininum concentrations of complete inhibition (MIC) and the switch attached to lacZ (d) that beta-galactosidase activity when the switch is attached to the lacZ gene is dose dependent.