Specific functions of the SOS response participate in survival to fluoroquinolones

• Online Access: http://hdl.handle.net/2047/D20194224

Persisters are bacterial cells that are able to tolerate antibiotic treatment without acquiring heritable resistance. It has previously been shown that the SOS-regulated toxin TisB induces persister formation by forming a channel in the inner membrane, dissipating the proton motive force and reducing the concentration of intracellular ATP. However, this mechanism is wasteful because depletion of the proton motive force will activate futile respiration and exhaust the cell's stored nutrients, leaving the cell unable to resuscitate. Previous studies have shown that DNA damage leads to the cessation of respiration, leading to the possibility that this phenomenon may complement the action of TisB. We are interested in discovering the cause of respiration shutdown, and identifying its role in survival to antibiotics. We have found that in both a recA deletion strain and lexA3 mutant strain DNA damage does not lead to cessation of respiration, indicating that this shutoff is dependent on an active SOS response. To identify the mechanism of respiration shutoff, two genetic screens were performed using an indicator of respiration to identify mutants lacking this shutoff phenotype. Analysis of the protein composition in respiring culture versus non-respiring cultures was performed using 2D gel electrophoresis. This information can be further used to increase our understanding on the mechanism behind this shutoff and its significance.