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
Prokaryotes E. coli