C2.

C2. Modulators of bacterial gene expression & stress responses

Bacterial stress responses affect the ability of the cells to produce biomolecules and act as biosensors. These systems act as a double‐edged sword: while their functionality is beneficial for the rapid growth of bacteria and generation of biomass, induction of the stress responses interferes with production of desired compounds of interest. One of these systems is the so‐called stringent response. Upon induction, this response leads to a dramatic increase in protease activity in bacteria, lowering the yields of recombinant protein production (17, 18). At the same time, loss of the stringent response functionality leads to a pleiotropic loss of cell fitness, including amino acid auxotrophy and unbalanced nucleotide metabolism (19, 20). In addition to its importance for biotechnology, the stringent response is of great medical interest due to its key role in antibiotic tolerance and bacterial virulence, making it a promising target for the development of novel antibacterial compounds (15, 21). Therefore, the development of bioengineering approaches for control of the stringent response using specific chemical probes is of great interest. New probes will be designed (Group 1), synthesized (Group 6) and tested in the bacterial systems (Group 2).