Bacterial senescence: stasis results in increased and differential oxidation of cytoplasmic proteins leading to developmental induction of the heat shock regulon.
Aging, or senescence, is the progressive deterioration of every bodily function over time. A fundamental question that applies to all life forms, including growth-arrested bacteria, is why growing older by necessity causes organisms to grow more fragile. In this work, we demonstrate that the levels of oxidized proteins is correlated to the age of a stationary-phase Escherichia coli culture; both disulfide bridge formation of a cytoplasmic leader-less alkaline phosphatase and protein carbonyl levels increase during stasis. The stasis-induced increase in protein oxidation is enhanced in cells lacking the global regulators OxyR and sigmas. Some proteins were found to be specifically susceptible to stasis-induced oxidation; notably several TCA cycle enzymes, glutamine synthetase, glutamate synthase, pyruvate kinase, DnaK, and H-NS. Evidence that oxidation of target proteins during stasis serves as the signal for stationary-phase, developmental, induction of the heat shock regulon is presented by demonstrating that this induction is mitigated by overproducing the superoxide dismutase SodA. In addition, cells lacking cytoplasmic superoxide dismutase activity exhibit superinduction of heat shock proteins. The possibility that oxidative sensitivity of TCA cycle enzymes serves as a feedback mechanism down-regulating toxic respiration is discussed.
Dukan
S
S
Department of Microbiology, Lund University, Lund, Sweden.
Nyström
T
T
D000469:Alkaline Phosphatase / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism / Q000502:physiology*; D003593:Cytoplasm / Q000378:metabolism / Q000502:physiology*; D004268:DNA-Binding Proteins; D004220:Disulfides; D004926:Escherichia coli / Q000254:growth & development* / Q000502:physiology*; D029968:Escherichia coli Proteins; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000502:physiology*; D009154:Mutation / Q000235:genetics; D010084:Oxidation-Reduction; D018085:Regulon / Q000502:physiology*; D012097:Repressor Proteins / Q000378:metabolism; D012808:Sigma Factor / Q000378:metabolism; D013482:Superoxide Dismutase / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D004220:Disulfides; D029968:Escherichia coli Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D012097:Repressor Proteins; D012808:Sigma Factor; D014157:Transcription Factors; C499299:oxyR protein, E coli; C069567:sigma factor KatF protein, Bacteria; C095500:SodA protein, Bacteria; D013482:Superoxide Dismutase; D000469:Alkaline Phosphatase; C063842:dnaK protein, E coli