Elevated Expression of Toxin TisB Protects Persister Cells against Ciprofloxacin but Enhances Susceptibility to Mitomycin C.
Daniel EdelmannFlorian H LeinbergerNicole E SchmidMarkus OberpaulTill F SchäberleBork A BerghoffPublished in: Microorganisms (2021)
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 Δ1-41 ΔistR) 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 Δ1-41 ΔistR 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, Δ1-41 ΔistR 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.
Keyphrases
- escherichia coli
- dna damage
- poor prognosis
- gene expression
- induced apoptosis
- cell cycle arrest
- transcription factor
- binding protein
- oxidative stress
- dna methylation
- single molecule
- cell proliferation
- pseudomonas aeruginosa
- dna repair
- drug resistant
- cell death
- endoplasmic reticulum stress
- long non coding rna
- magnetic resonance imaging
- magnetic resonance
- nucleic acid
- biofilm formation
- high glucose
- cell free
- cystic fibrosis
- wild type
- multidrug resistant
- living cells
- heat shock protein
- heat stress