The Old Yellow Enzyme OfrA Fosters Survival Affecting Thiol-Dependent Redox Homeostasis.

Old yellow enzymes (OYEs) are widely found in the bacterial, fungal, and plant kingdoms but absent in humans and have been used as biocatalysts for decades. However, OYEs' physiological function in bacterial stress response and infection situations remained enigmatic. As a pathogen, the Gram-positive bacterium adapts to numerous stress conditions during pathogenesis. Here, we show that in genome, two paralogous genes ( and ) encode for two OYEs. We conducted a bioinformatic analysis and found that is conserved among all publicly available representative staphylococcal genomes and some Firmicutes. Expression of is induced by electrophilic, oxidative, and hypochlorite stress in . Furthermore, contributes to survival against reactive electrophilic, oxygen, and chlorine species (RES, ROS, and RCS) thiol-dependent redox homeostasis. At the host-pathogen interface, Δ has defective survival in macrophages and whole human blood and decreased staphyloxanthin production. Overall, our results shed the light onto a novel stress response strategy in the important human pathogen .