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Full-Text Articles in Life Sciences

Regulation Of The Escherichia Coli Hipba Toxin-Antitoxin System By Proteolysis, Sonja Hansen, Marin Vulić, Tien-Jui Yen, Maria A. Schumacher, Richard G. Brennan, Kim Lewis Jun 2013

Regulation Of The Escherichia Coli Hipba Toxin-Antitoxin System By Proteolysis, Sonja Hansen, Marin Vulić, Tien-Jui Yen, Maria A. Schumacher, Richard G. Brennan, Kim Lewis

Marin Vulić

Bacterial populations produce antibiotic-tolerant persister cells. A number of recent studies point to the involvement of toxin/antitoxin (TA) modules in persister formation. hipBA is a type II TA module that codes for the HipB antitoxin and the HipA toxin. HipA is an EF-Tu kinase, which causes protein synthesis inhibition and dormancy upon phosphorylation of its substrate. Antitoxins are labile proteins that are degraded by one of the cytosolic ATP-dependent proteases. We followed the rate of HipB degradation in different protease deficient strains and found that HipB was stabilized in a lon- background. These findings were confirmed in an in vitro …


Ciprofloxacin Causes Persister Formation By Inducing The Tisb Toxin In Escherichia Coli, Tobias Dörr, Marin Vulić, Kim Lewis May 2011

Ciprofloxacin Causes Persister Formation By Inducing The Tisb Toxin In Escherichia Coli, Tobias Dörr, Marin Vulić, Kim Lewis

Marin Vulić

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, …


Sos Response Induces Persistence To Fluoroquinolones In Escherichia Coli, Tobias Dörr, Kim Lewis, Marin Vulić May 2011

Sos Response Induces Persistence To Fluoroquinolones In Escherichia Coli, Tobias Dörr, Kim Lewis, Marin Vulić

Marin Vulić

Bacteria can survive antibiotic treatment without acquiring heritable antibiotic resistance. We investigated persistence to the fluoroquinolone ciprofloxacin in Escherichia coli. Our data show that a majority of persisters to ciprofloxacin were formed upon exposure to the antibiotic, in a manner dependent on the SOS gene network. These findings reveal an active and inducible mechanism of persister formation mediated by the SOS response, challenging the prevailing view that persisters are pre-existing and formed purely by stochastic means. SOS-induced persistence is a novel mechanism by which cells can counteract DNA damage and promote survival to fluoroquinolones. This unique survival mechanism may be …