1887

Abstract

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 , encoding the cAMP phosphodiesterase, leads to a dramatically increased resistance of to HOCl stress as well as to the unrelated hydrogen peroxide (HO) 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 , encoding the alternative sigma factor , which activates the general stress response in . 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 -overexpressing strains towards HOCl and HO stress. Our results demonstrate the close regulatory interplay between cellular cAMP levels, activity and oxidative stress resistance in .

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2009-05-01
2024-04-19
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