Journal article

Authors list: Edelmann, D; Leinberger, FH; Schmid, NE; Oberpaul, M; Schäberle, TF; Berghoff, BA

Publication year: 2021

Pages: 943-

Journal: Microorganisms

Volume number: 9

Issue number: 5

Open access status: Gold

DOI Link: https://doi.org/10.3390/microorganisms9050943

Publisher: MDPI

Abstract: 
Bacterial chromosomes harbor toxin-antitoxin (TA) systems, some of which are implicated in the formation of multidrug-tolerant persister cells. In Escherichia coli, toxin TisB from the tisB/istR-1 TA system depolarizes the inner membrane and causes ATP depletion, which presumably favors persister formation. Transcription of tisB is induced upon DNA damage due to activation of the SOS response by LexA degradation. Transcriptional activation of tisB is counteracted on the post-transcriptional level by structural features of tisB mRNA and RNA antitoxin IstR-1. Deletion of the regulatory RNA elements (mutant Delta 1-41 Delta istR) uncouples TisB expression from LexA-dependent SOS induction and causes a 'high persistence' (hip) phenotype upon treatment with different antibiotics. Here, we demonstrate by the use of fluorescent reporters that TisB overexpression in mutant Delta 1-41 Delta istR inhibits cellular processes, including the expression of SOS genes. The failure in SOS gene expression does not affect the hip phenotype upon treatment with the fluoroquinolone ciprofloxacin, likely because ATP depletion avoids strong DNA damage. By contrast, Delta 1-41 Delta istR cells are highly susceptible to the DNA cross-linker mitomycin C, likely because the expression of SOS-dependent repair systems is impeded. Hence, the hip phenotype of the mutant is conditional and strongly depends on the DNA-damaging agent.

Harvard Citation style: Edelmann, D., Leinberger, F., Schmid, N., Oberpaul, M., Schäberle, T. and Berghoff, B. (2021) Elevated Expression of Toxin TisB Protects Persister Cells against Ciprofloxacin but Enhances Susceptibility to Mitomycin C, Microorganisms, 9(5), p. 943. https://doi.org/10.3390/microorganisms9050943

APA Citation style: Edelmann, D., Leinberger, F., Schmid, N., Oberpaul, M., Schäberle, T., & Berghoff, B. (2021). Elevated Expression of Toxin TisB Protects Persister Cells against Ciprofloxacin but Enhances Susceptibility to Mitomycin C. Microorganisms. 9(5), 943. https://doi.org/10.3390/microorganisms9050943