The role of Escherichia coli YrbB in the lethal action of quinolones

To explore bacterial cellular factors that protect against the lethal effect of antimicrobial stress as potential targets of antimicrobial potentiators, the role of Escherichia coli YrbB in protecting cells from quinolone-mediated cell death was studied. A set of isogenic strains containing different mutations in stress response genes of E. coli was constructed by P1-mediated transduction. The susceptibility of these strains to the lethal action of quinolones was determined by measuring viable colony counts on agar plates after treatment with quinolones under various conditions. A yrbB mutation rendered E. coli cells more susceptible to the lethal action of quinolones under conditions in which bacteriostatic susceptibility was unaffected. YrbB worked in both lethal pathways of quinolone action. Hydroxyl radical accumulation was required for nalidixic acid-mediated killing; however, in the absence of functional YrbB there was an additional mechanism through which nalidixic acid could kill cells independently of hydroxyl radical action. The E. coli chromosomal toxin-antitoxin system ChpB, but not the SOS system, was found to be involved in the hydroxyl radical-independent lethal mechanism. In addition, proteases ClpP and Lon were also involved in the action of YrbB. Besides quinolones, YrbB also played a protective role in cellular responses to other stressors, such as mitomycin C, ultraviolet light and hydrogen peroxide. YrbB played a protective role in the lethal action of quinolones through a hydroxyl radical-independent and toxin-antitoxin-dependent mechanism, which makes it a potential target for antimicrobial enhancement.