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Title 

Fumarate-mediated persistence of Escherichia coli against antibiotics

Authors 

J S KimD H ChoP HeoS C JungM ParkE J OhJ SungP J KimS C LeeDae-Hee LeeS LeeC H LeeD ShinY S JinD H Kweon

Publisher 

American Society for Microbiology

Issue Date 

2016

Citation 

Antimicrobial Agents and Chemotherapy, vol. 60, no. 4, pp. 2232-2240

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) in Escherichia coli led to a higher frequency of persister formation. The persister frequency of E. coli was 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-related hipA7 mutation indicated that surplus fumarate markedly elevated the E. coli persister frequency. An E. coli strain 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 that SDH and FRD represent a paired system that gives rise to and maintains E. coli persisters by producing and utilizing fumarate, respectively.

ISSN 

0066-4804

Link 

http://dx.doi.org/10.1128/AAC.01794-15

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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