title: Bacterial persisters tolerate antibiotics by not producing hydroxyl radicals.
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.
authors.affiliation: School of Life Science and Biotechnology and Center for Human Interface Nano Technology, Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, South Korea.
authors.forename: Jun-Seob
authors.initials: JS
authors.lastname: Kim
authors.forename: Paul
authors.initials: P
authors.lastname: Heo
authors.forename: Tae-Jun
authors.initials: TJ
authors.lastname: Yang
authors.forename: Ki-Sung
authors.initials: KS
authors.lastname: Lee
authors.forename: Yong-Su
authors.initials: YS
authors.lastname: Jin
authors.forename: Sung-Koo
authors.initials: SK
authors.lastname: Kim
authors.forename: Dongwoo
authors.initials: D
authors.lastname: Shin
authors.forename: Dae-Hyuk
authors.initials: DH
authors.lastname: Kweon
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D017665:Hydroxyl Radical / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D017665:Hydroxyl Radical