Investigating the Involvement of Post-Treatment Growth Related Events on Fluoroquinolone Persistence

Abstract

Bacterial persisters are a small subpopulation of bacteria that exhibit tolerance to antibiotic treatment followed by a return to a viable reproducing state after the removal of the antibiotic. As such, persister cells are thought to be associated with relapses of infections following seemingly successful treatment.1 The cellular mechanisms responsible for persister metabolism, which includes halting growth when the antibacterial stressor is present, maintaining the culturability of the cell during its period of stasis, and the resumption of growth following the removal of the stressor, are not completely understood at this time. To study these conditions, use of model persisters, or cells whose growth can be inhibited by toxin accumulation were employed. The goal of this project is to understand the varied tolerance to antibiotic treatment between two such model persister cell lines: HipA and MazF. Both persister cell lines demonstrate comparable tolerance to the β-lactam ampicillin, however, when treated with the fluoroquinolone ofloxacin, the HipA cell line appears to be much more susceptible. In understanding why this differing tolerance occurs, future work can identify cellular mechanisms associated with persister metabolism and to apply those findings to developing more effective treatments for combating bacterial persistence. The findings of this study demonstrate that even when growth-inhibited, the HipA strain exhibits a susceptibility to fluoroquinolone treatment that is not found in the MazF strain, however both strains demonstrate similar tolerance levels to β-lactam treatment.