Bacteria produce persisters, a small subpopulation of cells that neither grow nor die in the presence of antibiotics. Persisters are tolerant against exposure to multiple antibiotics and they likely contribute to the relapse of bacterial infections after antibiotic therapy. The mechanism of persister formation is unknown, although several studies have pointed towards redundancy in persister formation mechanisms and the possible involvement of chromosomal toxin-antitoxin modules.
While studying the genetic requirements for Escherichia coli persister survival after exposure to the DNA damaging antibiotic ciprofloxacin, we found that persister formation was an adaptive response to the antibiotic. Survivors to ciprofloxacin exhibited low levels of SOS induction and their survival depended largely on the SOS-inducible small toxic peptide TisB. Ectopic overproduction of TisB decreased proton motive force and induced growth arrest and multidrug tolerance. Further, synthesized TisB peptide formed an anion-selective pore in an artificial lipid bilayer system. These results suggest that TisB acts as an uncoupler of oxidative phosphorylation after induction of the SOS response.
These results challenge the common view of persisters as a metabolically inactive entity and show that persistence is in part an inducible response specific to a certain stress.
|Commitee:||Epstein, Slava S., Godoy, Veronica, Sonenshein, Abraham L., Vulic, Marin|
|School Location:||United States -- Massachusetts|
|Source:||DAI-B 71/11, Dissertation Abstracts International|
|Keywords:||Adaptive tolerance, Oxidative phosphorylation, Persisters, SOS response|
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