Reactive Oxygen Species Production Is a Major Factor Directing the Postantibiotic Effect of Fluoroquinolones in Streptococcus pneumoniae

We studied the molecular mechanisms involved in the postantibiotic effect of the fluoroquinolones levofloxacin and moxifloxacin in Wild-type strain R6 had postantibiotic effects of 2.05 ± 0.10 h (mean ± standard deviation [SD]) and 3.23 ± 0.45 h at 2.5× and 10× MIC of levofloxacin, respectively. Moxifloxacin exhibited lower effects of 0.87 ± 0.1 and 2.41 ± 0.29 h at 2.5× and 10× MIC, respectively. Fluoroquinolone-induced chromosome fragmentation was measured at equivalent postantibiotic effects for levofloxacin (2.5× MIC) and moxifloxacin (10× MIC). After 2 h of drug removal, reductions were approximately 7-fold for levofloxacin and 3-fold for moxifloxacin, without further decreases at later times. Variations in reactive oxygen species production were detected after 4 to 6 h of drug withdrawals, with decreases ≥400-fold for levofloxacin and ≥800-fold for moxifloxacin at 6 h. In accordance, after 4 to 6 h of drug withdrawal, the levofloxacin-induced upregulation of the operon, introducing iron in the bacteria, decreased up to 2- to 3-fold, and the moxifloxacin-induced upregulation of several genes involved in the production of pyruvate was reduced 3- to 7-fold. In accordance, lower postantibiotic effects (up to 1 h) were observed in strain R6 Δ , lacking the main enzyme involved in oxygen peroxide production, than in R6. Although no change in the recovery of chromosome fragmentation was observed between R6 and R6 Δ , 3.5 × 10 -fold lower reactive oxygen species production was observed in R6 Δ , without changes after drug removal. These results show that reactive oxygen species are the main factors directing the postantibiotic effect of levofloxacin and moxifloxacin in .