B1.

The global increase in antibiotic resistance requires (i) improvements to current antibacterial therapies and (ii) development of new antibacterial compounds. Several key issues concerning the mechanisms of infection and antibiotic action have only recently received wider attention. Firstly, genetically homogenous bacterial populations can contain phenotypically heterogeneous cells that have different roles in the infection process and respond differently to antibiotic treatment (15). Secondly, during infection bacteria localize into the heterogeneous and structured environments such as biofilms and intracellular space (16). The bulk physical‐ chemical measurements of antibiotic concentrations made in different organs might not reflect the active antibiotic concentrations encountered by bacteria. We are developing bacterial reporter cells that can be used for: (i) Identifying the bacterial physiological states during the infection process at the single cell level, and (ii) estimating antibiotic concentrations that single bacteria encounter during treatment. These reporter systems can potentially guide both the development of better dosing regimens for current antibiotics and in the development of new antibiotics. Several antibiotic candidates / derivatives will be compared in the biosensor systems developed (Group 2). Based on the information acquired new potential antibiotic structures will be designed by in silico experiments (Group 1) and synthesized (Group 6) and tested (Group 2).