Contribution of reactive oxygen species to pathways of quinolone-mediated bacterial cell death

Xiuhong Wang, Xilin Zhao, Muhammad Malik, Karl Drlica

Research output: Contribution to journalArticlepeer-review

106 Scopus citations


Background: Quinolone-mediated death of Escherichia coli has been proposed to occur by two pathways. One is blocked by inhibitors of protein synthesis; the other is not. It is currently unknown how these two pathways fit with the recent observation that hydroxyl radical accumulation is associated with quinolone lethality. Methods: E. coli was treated with thiourea plus 2,2′-bipyridyl to block hydroxyl radical accumulation, and the effect on quinolone lethality was measured for quinolones that distinguished the two lethal pathways: oxolinic acid requires protein synthesis to kill E. coli, while PD161144, a C-8-methoxy fluoroquinolone, does not. The lethal activity of another fluoroquinolone, moxifloxacin, was partially blocked by the presence of chloramphenicol, an inhibitor of protein synthesis. That feature made it possible to determine whether the effects of chloramphenicol and thiourea plus 2,2′-bipyridyl were additive. Results: Lethal activity of oxolinic acid was completely blocked by thiourea plus 2,2′-bipyridyl and by chloramphenicol. In contrast, PD161144 lethality was unaffected by these treatments. With moxifloxacin, both chloramphenicol and thiourea plus 2,2′-bipyridyl separately exhibited the same partial inhibition of quinolone lethality. No additivity in protection from moxifloxacin lethality was observed when thiourea, 2,2′-bipyridyl and chloramphenicol were combined and compared with the effect of chloramphenicol or thiourea plus 2,2′-bipyridyl used separately. Conclusions: Inhibitor studies indicated that hydroxyl radical action contributes to quinolone-mediated cell death occurring via the chloramphenicol-sensitive lethal pathway but not via the chloramphenicol-insensitive pathway.

Original languageEnglish (US)
Article numberdkp486
Pages (from-to)520-524
Number of pages5
JournalJournal of Antimicrobial Chemotherapy
Issue number3
StatePublished - Jan 12 2010

All Science Journal Classification (ASJC) codes

  • Microbiology (medical)
  • Pharmacology (medical)
  • Infectious Diseases
  • Pharmacology


  • 2,2′-bipyridyl
  • 8-methoxy fluoroquinolone
  • Hydoxyl radical
  • Oxolinic acid
  • Thiourea


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