Scientists have identified unforeseen mechanisms by which quinolones - a family of broad-spectrum antibiotics among the most widely prescribed - induce bacterial cell death.
The study is published online this week in Molecular Systems Biology.
It is well-known that quinolones inhibit bacterial DNA gyrase - an enzyme essential to DNA replication - and induce cell death by stimulating DNA damage, impeding lesion repair and blocking replication processes. Using a systems biology approach, Jim Collins and colleagues reveal that, in addition to the expected DNA damage response, gyrase inhibition surprisingly triggers a genetic program characteristic of responses to oxidative stress and promotes the generation of deleterious hydroxyl radicals.
The authors confirm their findings by showing that chemical or genetic prevention of gyrase inhibitor-induced oxidative damage protects from the bactericidal action of quinolone antibiotics. This work will facilitate the identification of antibacterial therapies with improved bactericidal activity.
http://www.nature.com/msb and http://www.bu.edu