| RRC ID |
53700
|
| Author |
Robinson JL, Brynildsen MP.
|
| Title |
An ensemble-guided approach identifies ClpP as a major regulator of transcript levels in nitric oxide-stressed Escherichia coli.
|
| Journal |
Metab Eng
|
| Abstract |
The importance of NO(∙) to immunity is highlighted by the diversity of pathogens that require NO(∙)-defensive systems to establish infections. Proteases have been identified to aid pathogens in surviving macrophage attack, inspiring us to investigate their role during NO(∙) stress in Escherichia coli. We discovered that the elimination of ClpP largely impaired NO(∙) detoxification by E. coli. Using a quantitative model of NO(∙) stress, we employed an ensemble-guided approach to identify the underlying mechanism. Iterations of in silico analyses and corresponding experiments identified the defect to result from deficient transcript levels of hmp, which encodes NO(∙) dioxygenase. Interestingly, the defect was not confined to hmp, as ΔclpP imparted widespread perturbations to the expression of NO(∙)-responsive genes. This work identified a target for anti-infective therapies based on disabling NO(∙) defenses, and demonstrated the utility of model-based approaches for exploring the complex, systems-level stress exerted by NO(∙).
|
| Volume |
31
|
| Pages |
22-34
|
| Published |
2015-9-1
|
| DOI |
10.1016/j.ymben.2015.06.005
|
| PII |
S1096-7176(15)00073-7
|
| PMID |
26112956
|
| MeSH |
Biocatalysis
Dihydropteridine Reductase / genetics*
Endopeptidase Clp / physiology*
Escherichia coli / genetics*
Escherichia coli / metabolism
Escherichia coli Proteins / genetics*
Escherichia coli Proteins / physiology*
Hemeproteins / genetics*
NADH, NADPH Oxidoreductases / genetics*
Nitric Oxide / metabolism*
Promoter Regions, Genetic
RNA, Messenger / analysis*
Sequence Analysis, RNA
Stress, Physiological
Transcription, Genetic
|
| IF |
7.263
|
| Times Cited |
15
|
| Resource |
| Prokaryotes E. coli |
|
