Transcription factor OxyR regulates peroxidase levels to enhance Brucella's defense against oxidative stress.

The host defense system produces high levels of oxidation products, including reactive oxygen species (ROS) and reactive nitrogen species (RNS), which disrupt bacterial metabolism and exert lethal effects. Crucially, Brucella counteracts oxidative stress by upregulating antioxidant enzymes-such as superoxide dismutase, catalase, and peroxidase. Central to this defense is OxyR, a peroxide-sensing transcriptional regulator that orchestrates antioxidant enzyme expression to mitigate oxidative damage. To define OxyR's role in Brucella homeostasis and host interactions, we constructed oxyR deletion and complemented strains using homologous recombination. Our study evaluated OxyR's impact on growth, stress responses (particularly oxidative stress), intracellular survival, and modulation of host inflammation. Results revealed that oxyR deletion caused significant growth retardation and reduced tolerance to acid stress, polymyxin B, and oxidative stress, concurrently downregulating both expression and activity of key antioxidant enzymes. Although intracellular survival within murine macrophages remained unaffected, oxyR deletion substantially suppressed critical inflammatory cytokine expression. In summary, OxyR is essential for optimal growth and stress resistance, exhibiting dual functionality in mitigating oxidative damage and modulating host inflammatory responses. These findings provide novel insights into Brucella immune evasion strategy.