title: Fumarate-Mediated Persistence of Escherichia coli against Antibiotics.
abstract: Bacterial persisters are a small fraction of quiescent cells that survive in the presence of lethal concentrations of antibiotics. They can regrow to give rise to a new population that has the same vulnerability to the antibiotics as did the parental population. Although formation of bacterial persisters in the presence of various antibiotics has been documented, the molecular mechanisms by which these persisters tolerate the antibiotics are still controversial. We found that amplification of the fumarate reductase operon (FRD) inEscherichia coliled to a higher frequency of persister formation. The persister frequency ofE. coliwas increased when the cells contained elevated levels of intracellular fumarate. Genetic perturbations of the electron transport chain (ETC), a metabolite supplementation assay, and even the toxin-antitoxin-relatedhipA7mutation indicated that surplus fumarate markedly elevated theE. colipersister frequency. AnE. colistrain lacking succinate dehydrogenase (SDH), thereby showing a lower intracellular fumarate concentration, was killed ∼1,000-fold more effectively than the wild-type strain in the stationary phase. It appears thatSDHandFRDrepresent a paired system that gives rise to and maintainsE. colipersisters by producing and utilizing fumarate, respectively.
authors.affiliation: Department of Genetic Engineering and Center for Human Interface Nano Technology, Sungkyunkwan University, Suwon, South Korea Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
authors.forename: Jun-Seob
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Genetic Engineering and Center for Human Interface Nano Technology, Sungkyunkwan University, Suwon, South Korea.
authors.forename: Da-Hyeong
authors.initials: DH
authors.lastname: Cho
authors.affiliation: Department of Genetic Engineering and Center for Human Interface Nano Technology, Sungkyunkwan University, Suwon, South Korea.
authors.forename: Paul
authors.initials: P
authors.lastname: Heo
authors.affiliation: Department of Genetic Engineering and Center for Human Interface Nano Technology, Sungkyunkwan University, Suwon, South Korea.
authors.forename: Suk-Chae
authors.initials: SC
authors.lastname: Jung
authors.affiliation: Department of Genetic Engineering and Center for Human Interface Nano Technology, Sungkyunkwan University, Suwon, South Korea.
authors.forename: Myungseo
authors.initials: M
authors.lastname: Park
authors.affiliation: Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
authors.forename: Eun-Joong
authors.initials: EJ
authors.lastname: Oh
authors.affiliation: Asia Pacific Center for Theoretical Physics, Pohang, South Korea.
authors.forename: Jaeyun
authors.initials: J
authors.lastname: Sung
authors.affiliation: Asia Pacific Center for Theoretical Physics, Pohang, South Korea Department of Physics, POSTECH, Pohang, South Korea.
authors.forename: Pan-Jun
authors.initials: PJ
authors.lastname: Kim
authors.affiliation: Department of Genetic Engineering and Center for Human Interface Nano Technology, Sungkyunkwan University, Suwon, South Korea.
authors.forename: Suk-Chan
authors.initials: SC
authors.lastname: Lee
authors.affiliation: Biochemicals and Synthetic Biology Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea.
authors.forename: Dae-Hee
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Bioscience and Biotechnology, Konkuk University, Seoul, South Korea.
authors.forename: Sarah
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Bioscience and Biotechnology, Konkuk University, Seoul, South Korea.
authors.forename: Choong Hwan
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, South Korea.
authors.forename: Dongwoo
authors.initials: D
authors.lastname: Shin
authors.affiliation: Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA ysjin@illinois.edu dhkweon@skku.edu.
authors.forename: Yong-Su
authors.initials: YS
authors.lastname: Jin
authors.affiliation: Department of Genetic Engineering and Center for Human Interface Nano Technology, Sungkyunkwan University, Suwon, South Korea ysjin@illinois.edu dhkweon@skku.edu.
authors.forename: Dae-Hyuk
authors.initials: DH
authors.lastname: Kweon
mesh_terms: D000667:Ampicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D002952:Citric Acid Cycle / Q000187:drug effects / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D004579:Electron Transport / Q000187:drug effects / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D005650:Fumarates / Q000378:metabolism; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D015723:Gene Library; D007612:Kanamycin / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009643:Norfloxacin / Q000494:pharmacology; D009876:Operon; D013385:Succinate Dehydrogenase / Q000172:deficiency / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D005650:Fumarates; D007612:Kanamycin; D000667:Ampicillin; C032005:fumaric acid; D013385:Succinate Dehydrogenase; D009643:Norfloxacin
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