Escherichia coli type I toxin TisB exclusively controls proton depolarization following antibiotic induced DNA damage.

Bacterial toxin-antitoxin (TA) systems are genetic loci where the antitoxin gene product helps to control the expression or activity of the toxin gene product. Type I TA systems typically produce hydrophobic peptides that often localize to the inner membrane of bacteria. These amphipathic peptides can then potentially affect ion flows across the inner membrane. Here, we show that several type I toxins from Escherichia coli can affect depolarization, whereas tisB exclusively controls the depolarization of the proton gradient. tisB has been linked to persister cell formation following treatment with the antibiotic ciprofloxacin and tisB-istR has been implicated in the control of proton depolarization following treatment with ofloxacin. These results suggest that tisB could initiate the formation of persister cells by fully dissipating the proton gradient and that most of the electrical gradient greatly limiting ATP production following antibiotic-induced DNA damage.