TY - JOUR
T1 - Enhanced antibiotic resistance development from fluoroquinolone persisters after a single exposure to antibiotic
AU - Barrett, Theresa C.
AU - Mok, Wendy W.K.
AU - Murawski, Allison M.
AU - Brynildsen, Mark P.
N1 - Funding Information:
We thank Zemer Gitai, Ned Wingreen, Thomas Silhavy, Katherine Volzing, Maxwell Wilson, Benjamin Bratton, Wei Wang, Jessica Wiggins, Ling Guo, Jennifer Miller, Daniel Sanchez, Lance Parsons, Gary Laevsky (Nikon Center of Excellence in the Princeton Confocal Imaging Facility), Christina DeCoste (Princeton Flow Cytometry Resource Center), and Sandra Aedo for assistance and advice. We thank the National BioResource Project (NIG, Japan) for distribution of the Keio collection. This work was supported by the NIAID of the NIH (T.C.B.: F30AI114163, M.P.B: R21AI115075, R01AI130293), the Charles H. Revson Foundation (W.W.K.M.: Fellowship in Biomedical Science), and Princeton University (M.P.B.: startup funds). This content is solely the responsibility of the authors and does not necessarily represent the views of the funding agencies.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-019-09058-4
DO - 10.1038/s41467-019-09058-4
M3 - Article
C2 - 30862812
AN - SCOPUS:85062855423
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1177
ER -