Ciprofloxacin causes persister formation by inducing the TisB toxin in Escherichia coli

Title:
Ciprofloxacin causes persister formation by inducing the TisB toxin in Escherichia coli
Creator:
Dörr, Tobias (Author)
Vulić, Marin (Author)
Lewis, Kim (Author)
Language:
English
Publisher:
Public Library of Science Biology
Copyright date:
2010
Type of resource:
Text
Genre:
Articles
Format:
electronic
Digital origin:
born digital
Abstract/Description:
Bacteria induce stress responses that protect the cell from lethal factors such as DNA-damaging agents. Bacterial populations also form persisters, dormant cells that are highly tolerant to antibiotics and play an important role in recalcitrance of biofilm infections. Stress response and dormancy appear to represent alternative strategies of cell survival. The mechanism of persister formation is unknown, but isolated persisters show increased levels of toxin/antitoxin (TA) transcripts. We have found previously that one or more components of the SOS response induce persister formation after exposure to a DNA-damaging antibiotic. The SOS response induces several TA genes in Escherichia coli. Here, we show that a knockout of a particular SOS-TA locus, tisAB/istR, had a sharply decreased level of persisters tolerant to ciprofloxacin, an antibiotic that causes DNA damage. Step-wise administration of ciprofloxacin induced persister formation in a tisAB-dependent manner, and cells producing TisB toxin were tolerant to multiple antibiotics. TisB is a membrane peptide that was shown to decrease proton motive force and ATP levels, consistent with its role in forming dormant cells. These results suggest that a DNA damage-induced toxin controls production of multidrug tolerant cells and thus provide a model of persister formation.
Comments:
Originally published in PLoS Biology, 8(2): e1000317.
doi:10.1371/journal.pbio.1000317
This work was supported by grants 3R01 GM061162 and 3R01GM061162-10S1 from the National Institutes of Health (NIH) Institute of General Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Subjects and keywords:
Antibiotics
Bacterial antitoxins
Bacterial toxins
Drug resistance in microorganisms
Ciprofloxacin
bacteria
persisters
stress response
toxin/antitoxin (TA) transcripts
Bacteriology
Permanent Link:
http://hdl.handle.net/2047/d20000891

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