Fumarate-Mediated Persistence of Escherichia coli against Antibiotics.
Antimicrob Agents Chemother
; 60(4): 2232-40, 2016 Apr.
Article
in En
| MEDLINE
| ID: mdl-26810657
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 â¼1,000-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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Succinate Dehydrogenase
/
Bacterial Proteins
/
Gene Expression Regulation, Bacterial
/
Drug Resistance, Multiple, Bacterial
/
Escherichia coli
/
Anti-Bacterial Agents
Language:
En
Journal:
Antimicrob Agents Chemother
Year:
2016
Document type:
Article
Affiliation country:
United States