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bioRxiv · 10.1101/2022.07.19.500589

The catalase contributes to microaerophilic H2O2 priming and the peroxiredoxins AhpC, Tpx and Bcp confer resistance to organic hydroperoxides in Staphylococcus aureus

Abstract

Staphylococcus aureus is a major human pathogen, which has to cope with oxidative stress as part of the host innate immune defense under macrophage and neutrophil infections. In this study, we have investigated the role of the catalase KatA and the peroxiredoxins AhpC, Tpx, and Bcp for priming and resistance under oxidative stress in S. aureus during aerobic and microaerophilic growth. The results revealed that S. aureus is resistant to high doses of up-to 100 mM H2O2 during the aerobic growth. While KatA is essential for this high aerobic H2O2 resistance, the peroxiredoxin AhpC contributes to detoxification of 0.4 mM H2O2 in the absence of KatA. In addition, AhpC, Tpx and Bcp were shown to be required for detoxification of cumene hydroperoxide (CHP) and regeneration of the reduced state of the bacillithiol (BSH) redox potential during recovery from CHP stress in S. aureus. The high H2O2 tolerance of aerobic S. aureus cells was associated with priming by endogenous H2O2 levels, which was supported by an oxidative shift of the basal level of EBSH (-291 mV) compared to that in microaerophilic cells (-310 mV). In contrast, S. aureus can be primed by sub-lethal doses of 100 {micro}M H2O2 during the microaerophilic growth to acquire an improved resistance towards the otherwise lethal triggering stimulus of 10 mM H2O2. This microaerophilic priming was dependent on increased katA transcription and elevated KatA activity, whereas aerobic control cells showed already constitutive high KatA activity. Thus, KatA is the major player contributing to the high H2O2 resistance of aerobic cells and to microaerophilic H2O2 priming to survive the subsequent lethal triggering doses of H2O2, allowing the adaptation of S. aureus to oxidative stress under infections in different oxygen environments.

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BibTeXRIS

Linzner, N., Loi, V. V., Antelmann, H.. 2022-07-20. The catalase contributes to microaerophilic H2O2 priming and the peroxiredoxins AhpC, Tpx and Bcp confer resistance to organic hydroperoxides in Staphylococcus aureus. https://doi.org/10.1101/2022.07.19.500589

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