Ferric uptake regulator
(Fur) of <i>Helicobacter pylori</i> is a global regulator
that is important for bacterial colonization and survival within the
gastric mucosa. <i>H. pylori</i> Fur (<i>Hp</i>Fur) is unique in its ability to regulate gene expression in both
metal-bound (holo-Fur) and metal-free (apo-Fur) forms. Bismuth-based
drugs are widely used for the treatment of <i>H. pylori</i> infection. However, the mechanism of action of bismuth drug was
not fully understood. Recently, it has been reported that bismuth
drugs could interfere with the bacterial ferric uptake pathway and
inhibit bacterial growth, implying intrinsic correlation between bismuth
drug and bacterial iron metabolism. Herein, we demonstrate that Bi(III)
binds to <i>Hp</i>Fur protein specifically at the physiologically
important S1 site, which further leads to protein oligomerization
and loss of DNA binding capability. The targeting of <i>Hp</i>Fur by bismuth drugs significantly reduced transcription levels of
its regulated genes, which are crucial for bacterial physiology and
metabolism. Our studies present direct evidence that perturbation
of iron metabolism in <i>H. pylori</i> by bismuth might
serve as one of the mechanisms for the antimicrobial activity of bismuth
drugs
