ROS-induced allosteric modulation of NikR promotes <i>helicobacter pylori</i> biofilm formation by attenuating FlgR-dependent inhibition of the molybdate transport system

<i>Helicobacter pylori</i> biofilm formation is crucial for its persistence and transmission, constituting a notable public health concern. Understanding the regulatory mechanisms driving biofilm initiation is vital for developing effective control strategies. This study reveals a previously uncharacterized regulatory mechanism where reactive oxygen species (ROS) promote <i>H. pylori</i> biofilm formation by modulating the key flagellar regulator FlgR and the molybdate transport system ModABD. We demonstrate that FlgR acts as a repressor of biofilm development. Mechanistically, FlgR inhibits the transcription of the <i>modABD</i> operon, essential for biofilm formation, by suppressing the activity of sigma factor σ²⁸. Crucially, we identify the nickel-responsive regulator NikR as a repressor of <i>flgR</i> expression. ROS induce a conformational change in NikR, converting it to its DNA-binding holo-form, which directly binds the <i>flgR</i> promoter and represses its expression. This repression alleviates FlgR-mediated inhibition of σ²⁸, thereby de-repressing the <i>modABD</i> operon and facilitating the transition from planktonic to biofilm growth. Our findings uncover a previously unknown ROS-NikR-FlgR-σ²⁸-ModABD signaling axis governing <i>H. pylori</i> biofilm formation.