FlhF interacts with TonB2 to defend against oxidative stress in Campylobacter jejuni

Campylobacter jejuni is the leading cause of bacterial foodborne diarrheal disease worldwide. Despite its microaerophilic nature, C. jejuni is ubiquitous in aerobic environments and must possess specific adaptation mechanisms against oxidative stress. Here, we identified a novel role for FlhF, a GTPase essential for proper flagellar assembly, in promoting resistance to hydrogen peroxide (H₂O₂). Comparative transcriptomic analysis under H₂O₂ stress revealed that deletion of flhF leads to significant downregulation of oxidative stress-related genes. FlhF directly interacts with TonB2, an iron transport-associated protein, via its B and N domains. Codeletion of flhF and tonB2 leads to increased sensitivity to H₂O₂, suggesting a synergistic interaction. Moreover, the FlhF-TonB2 interaction promotes H₂O₂ detoxification, potentially by modulating intracellular iron homeostasis and influencing redox processes. Together, these findings reveal a novel function of FlhF in the oxidative stress response of C. jejuni, offering new insights into flagella-associated defense mechanisms in this pathogen.