Bicyclomycin generates ROS and blocks cell division inEscherichia coli

Abstract

AbstractThe role of reactive oxygen species (ROS) in the killing exerted by antibiotics on bacteria is debated. Evidences attribute the part of toxicity of many antibiotics to their ability to generate ROS by interfering with cellular metabolism, but some studies dismiss the role of ROS. Bicyclomycin (BCM) is a broad-spectrum antibiotic that is the only known compound to inhibitE. colitranscription terminator factor Rho with no known other cellular targets. In the present study, we addressed this question by checking whether the induction of oxidative stress could explain the increased sensitivity to Bicyclomycin in thehnsdeleted strain even in Δkilbackground inE. coli. BCM evoked the generation of ROS inE. colicells. BCM is known to cause the cell filamentation phenotype inE. coli.Performing fluorescence microscopic analysis, we show that bicyclomycin-dependent cell filamentation is associated with SOS response. RecA- GFP filaments were found to colocalize with the damaged DNA sites in the cell. Further analyzes revealed that the genomic DNA was partitioned but the cell septum formation was severely affected under BCM treatment. Furthermore, we observed biofilm formation byE. coliafter BCM treatment. We hypothesize that ROS production after BCM treatment could lead to cell filamentation in bacteria. A better understanding of the mode of toxicity of BCM will help us in designing better antibiotic treatment regimes for clinical practices, including combinatorial drug therapies. The cell filamentation phenotype observed after BCM treatment makes this antibiotic a promising drug for PAS therapy.