Enhanced antibiotic resistance development from fluoroquinolone persisters after a single exposure to antibiotic.

TitleEnhanced antibiotic resistance development from fluoroquinolone persisters after a single exposure to antibiotic.
Publication TypeJournal Article
Year of Publication2019
AuthorsBarrett, TC, Mok, WWK, Murawski, AM, Brynildsen, MP
JournalNat Commun
Volume10
Issue1
Pagination1177
Date Published2019 03 12
ISSN2041-1723
KeywordsAnti-Bacterial Agents, DNA Damage, DNA-Directed DNA Polymerase, Drug Resistance, Bacterial, Escherichia coli, Escherichia coli Proteins, Microscopy, Fluorescence, Ofloxacin, Rec A Recombinases, SOS Response (Genetics), Time-Lapse Imaging
Abstract

Bacterial persisters are able to tolerate high levels of antibiotics and give rise to new populations. Persister tolerance is generally attributed to minimally active cellular processes that prevent antibiotic-induced damage, which has led to the supposition that persister offspring give rise to antibiotic-resistant mutants at comparable rates to normal cells. Using time-lapse microscopy to monitor Escherichia coli populations following ofloxacin treatment, we find that persisters filament extensively and induce impressive SOS responses before returning to a normal appearance. Further, populations derived from fluoroquinolone persisters contain significantly greater quantities of antibiotic-resistant mutants than those from untreated controls. We confirm that resistance is heritable and that the enhancement requires RecA, SOS induction, an opportunity to recover from treatment, and the involvement of error-prone DNA polymerase V (UmuDC). These findings show that fluoroquinolones damage DNA in persisters and that the ensuing SOS response accelerates the development of antibiotic resistance from these survivors.

DOI10.1038/s41467-019-09058-4
Alternate JournalNat Commun
PubMed ID30862812
PubMed Central IDPMC6414640
Grant ListR21AI115075 / NH / NIH HHS / United States
F30 AI114163 / AI / NIAID NIH HHS / United States
R01AI130293 / NH / NIH HHS / United States
F30AI114163 / NH / NIH HHS / United States
R21 AI115075 / AI / NIAID NIH HHS / United States
R01 AI130293 / AI / NIAID NIH HHS / United States