title: Reprogramming of Escherichia coli K-12 metabolism during the initial phase of transition from an anaerobic to a micro-aerobic environment.
abstract: BACKGROUND
  Many bacteria undergo transitions between environments with differing O₂ availabilities as part of their natural lifestyles and during biotechnological processes. However, the dynamics of adaptation when bacteria experience changes in O₂ availability are understudied. The model bacterium and facultative anaerobe Escherichia coli K-12 provides an ideal system for exploring this process.
  
  
  RESULTS
  Time-resolved transcript profiles of E. coli K-12 during the initial phase of transition from anaerobic to micro-aerobic conditions revealed a reprogramming of gene expression consistent with a switch from fermentative to respiratory metabolism. The changes in transcript abundance were matched by changes in the abundances of selected central metabolic proteins. A probabilistic state space model was used to infer the activities of two key regulators, FNR (O₂ sensing) and PdhR (pyruvate sensing). The model implied that both regulators were rapidly inactivated during the transition from an anaerobic to a micro-aerobic environment. Analysis of the external metabolome and protein levels suggested that the cultures transit through different physiological states during the process of adaptation, characterized by the rapid inactivation of pyruvate formate-lyase (PFL), a slower induction of pyruvate dehydrogenase complex (PDHC) activity and transient excretion of pyruvate, consistent with the predicted inactivation of PdhR and FNR.
  
  
  CONCLUSIONS
  Perturbation of anaerobic steady-state cultures by introduction of a limited supply of O₂ combined with time-resolved transcript, protein and metabolite profiling, and probabilistic modeling has revealed that pyruvate (sensed by PdhR) is a key metabolic signal in coordinating the reprogramming of E. coli K-12 gene expression by working alongside the O₂ sensor FNR during transition from anaerobic to micro-aerobic conditions.
authors: Department of Molecular Biology and Biotechnology, The Krebs Institute, University of Sheffield, Sheffield, United Kingdom.
authors: Eleanor W
authors: EW
authors: Trotter
authors: Matthew D
authors: MD
authors: Rolfe
authors: Andrea M
authors: AM
authors: Hounslow
authors: C Jeremy
authors: CJ
authors: Craven
authors: Michael P
authors: MP
authors: Williamson
authors: Guido
authors: G
authors: Sanguinetti
authors: Robert K
authors: RK
authors: Poole
authors: Jeffrey
authors: J
authors: Green
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects / Q000235:genetics; D000332:Aerobiosis; D000693:Anaerobiosis; D019149:Bioreactors; D046508:Culture Techniques; D004777:Environment; D048168:Escherichia coli K12 / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism; D005285:Fermentation / Q000187:drug effects / Q000235:genetics; D007506:Iron-Sulfur Proteins / Q000378:metabolism; D055442:Metabolome / Q000187:drug effects / Q000235:genetics; D010100:Oxygen / Q000494:pharmacology; D019289:Pyruvic Acid / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D013997:Time Factors; D059467:Transcriptome
chemical_list: D029968:Escherichia coli Proteins; C060704:FNR protein, E coli; D007506:Iron-Sulfur Proteins; C084955:PdhR protein, E coli; D012333:RNA, Messenger; D012097:Repressor Proteins; D019289:Pyruvic Acid; D010100:Oxygen