RRC ID 53701
著者 Mok WW, Orman MA, Brynildsen MP.
タイトル Impacts of global transcriptional regulators on persister metabolism.
ジャーナル Antimicrob Agents Chemother
Abstract Bacterial persisters are phenotypic variants with an extraordinary capacity to tolerate antibiotics, and they are hypothesized to be a main cause of chronic and relapsing infections. Recent evidence has suggested that the metabolism of persisters can be targeted to develop therapeutic countermeasures; however, knowledge of persister metabolism remains limited due to difficulties associated with isolating these rare and transient phenotypic variants. By using a technique to measure persister catabolic activity, which is based on the ability of metabolites to enable aminoglycoside (AG) killing of persisters, we investigated the role of seven global transcriptional regulators (ArcA, Cra, cyclic AMP [cAMP] receptor protein [CRP], DksA, FNR, Lrp, and RpoS) on persister metabolism. We found that removal of CRP resulted in a loss of AG potentiation in persisters for all metabolites tested. These results highlight a central role for cAMP/CRP in persister metabolism, as its perturbation can significantly diminish the metabolic capabilities of persisters and effectively eliminate the ability of AGs to eradicate these troublesome bacteria.
巻・号 59(5)
ページ 2713-9
公開日 2015-5-1
DOI 10.1128/AAC.04908-14
PII AAC.04908-14
PMID 25712354
PMC PMC4394825
MeSH Aminoglycosides / pharmacology Anti-Bacterial Agents / pharmacology* Bacterial Outer Membrane Proteins / genetics Bacterial Proteins / genetics Cyclic AMP Receptor Protein / genetics Drug Resistance, Multiple, Bacterial / genetics Escherichia coli / drug effects Escherichia coli / metabolism Escherichia coli Proteins / genetics Gentamicins / pharmacology Microbial Sensitivity Tests Repressor Proteins / genetics
IF 4.904
引用数 16
リソース情報
原核生物(大腸菌)