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Interplay of cellular cAMP levels, ^S activity and oxidative stress resistance in Escherichia coli

Evelyn Barth^1,

Katherine V. Gora^2,

Katharina M. Gebendorfer^1,3,

Florian Settele^2,

¹ Department Chemie, Biotechnologie, Technische Universität München, Lichtenbergstraße 4, 85747 Garching, Germany
² Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109-1048, USA
³ Center for Integrated Protein Science Munich (CiPS^M), 81377 Munich, Germany

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 (H₂O₂) 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 ^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 H₂O₂ stress. Our results demonstrate the close regulatory interplay between cellular cAMP levels, ^S activity and oxidative stress resistance in E. coli.

Correspondence
Jeannette Winter
jeannette.winter{at}ch.tum.de

These authors contributed equally to this work.

Present address: Deutsches Krebsforschungszentrum, Department Cell Cycle Control and Carcinogenesis, Im Neuenheimer Feld 242, 69121 Heidelberg, Germany.

Supporting supplementary material is available with the online version of this paper.