Bacterial persisters tolerate antibiotics by not producing hydroxyl radicals

Jun Seob Kim, Paul Heo, Tae Jun Yang, Ki Sung Lee, Yong Su Jin, Sung Koo Kim, Dongwoo Shin, Dae Hyuk Kweon

Research output: Contribution to journalArticlepeer-review

Abstract

In a phenomenon called persistence, small numbers of bacterial cells survive even after exposure to antibiotics. Recently, bactericidal antibiotics have been demonstrated to kill bacteria by increasing the levels of hydroxyl radicals inside cells. In the present study, we report a direct correlation between intracellular hydroxyl radical formation and bacterial persistence. By conducting flow cytometric analysis in a three-dimensional space, we resolved distinct bacterial populations in terms of intracellular hydroxyl radical levels, morphology and viability. We determined that, upon antibiotic treatment, a small sub-population of Escherichia coli survivors do not overproduce hydroxyl radicals and maintain normal morphology, whereas most bacterial cells were killed by accumulating hydroxyl radicals and displayed filamentous morphology. Our results suggest that bacterial persisters can be formed once they have transient defects in mediating reactions involved in the hydroxyl radical formation pathway. Thus, it is highly probable that persisters do not share a common mechanism but each persister cell respond to antibiotics in different ways, while they all commonly show lowered hydroxyl radical formation and enhanced tolerance to antibiotics.

Original languageEnglish (US)
Pages (from-to)105-110
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume413
Issue number1
DOIs
StatePublished - Sep 16 2011

Keywords

  • Antibiotics
  • Flow cytometer
  • Hydroxyl radical
  • Persistence
  • Resistance

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

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