Interplay of cellular cAMP levels, {sigma}S activity and oxidative stress resistance in Escherichia coli.
Hypochlorous acid (HOCl), the active ingredient of household bleach, functions as a powerful antimicrobial that is used not only in numerous industrial applications but also in mammalian host defence. Here we show that multicopy expression of cpdA, encoding the cAMP phosphodiesterase, leads to a dramatically increased resistance of Escherichia coli to HOCl stress as well as to the unrelated hydrogen peroxide (H(2)O(2)) stress. This general oxidative stress resistance is apparently caused by the CpdA-mediated decrease in cellular cAMP levels, which leads to the partial inactivation of the global transcriptional regulator cAMP receptor protein (CRP). Downregulation of CRP in turn causes the derepression of rpoS, encoding the alternative sigma factor sigma(S), which activates the general stress response in E. coli. We found that these highly oxidative stress-resistant cells have a substantially increased capacity to combat HOCl-mediated insults and to degrade reactive oxygen species. Mutational analysis revealed that the DNA-protecting protein Dps, the catalase KatE, and the exonuclease III XthA play the predominant roles in conferring the high resistance of rpoS-overexpressing strains towards HOCl and H(2)O(2) stress. Our results demonstrate the close regulatory interplay between cellular cAMP levels, sigma(S) activity and oxidative stress resistance in E. coli.
Department Chemie, Biotechnologie, Technische Universität München, Lichtenbergstraße 4, 85747 Garching, Germany.
Evelyn
E
Barth
Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109-1048, USA.
Katherine V
KV
Gora
Center for Integrated Protein Science Munich (CiPSM), 81377 Munich, Germany.|Department Chemie, Biotechnologie, Technische Universität München, Lichtenbergstraße 4, 85747 Garching, Germany.
Katharina M
KM
Gebendorfer
Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109-1048, USA.
Florian
F
Settele
Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109-1048, USA.
Ursula
U
Jakob
Center for Integrated Protein Science Munich (CiPSM), 81377 Munich, Germany.|Department Chemie, Biotechnologie, Technische Universität München, Lichtenbergstraße 4, 85747 Garching, Germany.
Jeannette
J
Winter
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D002373:Cyclic AMP Receptor Protein / Q000235:genetics / Q000378:metabolism; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006997:Hypochlorous Acid / Q000494:pharmacology; D018384:Oxidative Stress; D012808:Sigma Factor / Q000235:genetics / Q000378:metabolism*
D001426:Bacterial Proteins; D002373:Cyclic AMP Receptor Protein; D029968:Escherichia coli Proteins; D012808:Sigma Factor; C069567:sigma factor KatF protein, Bacteria; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases