Title | Enhanced antibiotic resistance development from fluoroquinolone persisters after a single exposure to antibiotic. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Barrett, TC, Mok, WWK, Murawski, AM, Brynildsen, MP |
Journal | Nat Commun |
Volume | 10 |
Issue | 1 |
Pagination | 1177 |
Date Published | 2019 Mar 12 |
ISSN | 2041-1723 |
Keywords | Anti-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 | <p>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.</p> |
DOI | 10.1038/s41467-019-09058-4 |
Alternate Journal | Nat Commun |
PubMed ID | 30862812 |
PubMed Central ID | PMC6414640 |
Grant List | R21AI115075 / 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 |