Sacrificial redox modulation by a secreted bacterial effector molecule mitigates oxidative stress and inflammation in vivo.

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Andersson T, Anwaar S, Fuentes-Lemus E, Allhorn M, Happonen L, Veitch M, Chew HY, Montes de Oca M, Tanner L, Brüggemann H, Nordenfelt P, Davies MJ, Wells JW, Lood R

Free Radic. Biol. Med. 240 (-) 339-346 [2025-12-01; online 2025-08-21]

Human-bacterial interactions play a crucial role in several essential aspects of life. Here, we describe how a secreted protein from the skin commensal Cutibacterium acnes, RoxP, functions as a sacrificial redox effector molecule that facilitates beneficial interactions with its human host by counteracting oxidative stress and reducing stress-induced inflammation. Using a combination of structural mapping, biophysical binding studies, and in vivo experiments, we demonstrate how RoxP contributes to skin homeostasis by serving as a target for oxidative attack and influencing cytokine signaling. To our knowledge, this is the first in vivo mechanistic description of a secreted prokaryotic effector molecule modulating host redox balance through sacrificial oxidation, providing evidence of its role as a health-promoting factor.

Structural Proteomics [Collaborative]

PubMed 40849000

DOI 10.1016/j.freeradbiomed.2025.08.038

Crossref 10.1016/j.freeradbiomed.2025.08.038

pii: S0891-5849(25)00925-6