AUTHOR=Ibrahim Eslam S. , Ohlsen Knut 

TITLE=The Old Yellow Enzyme OfrA Fosters Staphylococcus aureus Survival via Affecting Thiol-Dependent Redox Homeostasis

JOURNAL=Frontiers in Microbiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.888140

DOI=10.3389/fmicb.2022.888140

ISSN=1664-302X

ABSTRACT=<p>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 <italic>Staphylococcus aureus</italic> adapts to numerous stress conditions during pathogenesis. Here, we show that in <italic>S. aureus</italic> genome, two paralogous genes (<italic>ofrA</italic> and <italic>ofrB</italic>) encode for two OYEs. We conducted a bioinformatic analysis and found that <italic>ofrA</italic> is conserved among all publicly available representative staphylococcal genomes and some Firmicutes. Expression of <italic>ofrA</italic> is induced by electrophilic, oxidative, and hypochlorite stress in <italic>S. aureus</italic>. Furthermore, <italic>ofrA</italic> contributes to <italic>S. aureus</italic> survival against reactive electrophilic, oxygen, and chlorine species (RES, ROS, and RCS) <italic>via</italic> thiol-dependent redox homeostasis. At the host–pathogen interface, <italic>S. aureus</italic>Δ<italic>ofrA</italic> 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 <italic>S. aureus</italic>.</p>