Fumarate-Mediated Persistence of Escherichia coli against Antibiotics
| Autor: | Pan-Jun Kim, Da Hyeong Cho, Dae-Hee Lee, Jun Seob Kim, Choong Hwan Lee, Jaeyun Sung, Paul Heo, Dongwoo Shin, Suk Chae Jung, Myungseo Park, Eun Joong Oh, Dae-Hyuk Kweon, Suk Chan Lee, Sarah Lee, Yong Su Jin |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.drug_class Metabolite Citric Acid Cycle 030106 microbiology Population Antibiotics Microbial Sensitivity Tests Biology medicine.disease_cause Bacterial genetics Microbiology Electron Transport 03 medical and health sciences chemistry.chemical_compound Bacterial Proteins Fumarates Kanamycin Drug Resistance Multiple Bacterial Operon Escherichia coli medicine Pharmacology (medical) education Gene Library Pharmacology education.field_of_study Gene Expression Profiling Succinate dehydrogenase Gene Expression Regulation Bacterial Fumarate reductase Anti-Bacterial Agents Succinate Dehydrogenase Infectious Diseases chemistry Biochemistry Susceptibility biology.protein Ampicillin Intracellular Norfloxacin |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 60:2232-2240 |
| ISSN: | 1098-6596 0066-4804 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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