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Compartmentalized oxygen generation from hydrogen peroxide enables anaerobic oxidative phosphorylation and confers a fitness advantage

Created on 04 Aug 2026

Authors

Moning, S. U., Baertschi, Y., Heger, L., Hentschel, J., Kaegi, J., Friedrich, T., von Ballmoos, C.

Abstract

Hydrogen peroxide is a host-derived reactive oxygen species that invading bacteria must detoxify to overcome the host defence. It was previously proposed that cytoplasmic catalase converts this peroxide into molecular oxygen, allowing facultative anaerobes such as Escherichia coli and Salmonella to respire in oxygen-limited niches. Here, we experimentally test this mechanism by reconstituting a minimal system comprising bovine catalase and purified E. coli quinol oxidases in liposomes. We find that catalase-generated oxygen sustains quinol oxidation under anaerobic conditions, and the rapid consumption keeps the environment effectively oxygen-free. When F1FO ATP synthase is included into the proteoliposomes, the system generates a protonmotive force that drives ATP synthesis, with activity scaling with hydrogen peroxide concentration. Competition experiments at low peroxide concentrations demonstrate that compartmentalized oxygen production provides a decisive advantage, as liposomes lacking catalase are strongly outcompeted. All three terminal quinol oxidases of E. coli were tested and shown to support ATP synthesis in vitro, suggesting that bd-II involvement in vivo is likely due to regulation of gene expression rather than catalytic constraints. Together, our data show that intracellular oxygen generation from host-derived peroxide enables oxidative phosphorylation in globally anaerobic, electron-acceptor-limited environments such as the gut, thereby providing a mechanistic explanation for the observed fitness advantage.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 04 Aug 2026.

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