Iron is an essential nutrient for the growth of most bacteria. To obtain
iron, bacteria have developed specific
iron-transport systems located on the membrane surface to uptake
iron and
iron complexes such as
ferrichrome. Interference with the
iron-acquisition systems should be therefore an efficient strategy to suppress bacterial growth and
infection. Based on the chemical similarity of
iron and
ruthenium, we used a Ru(II) complex R-825 to compete with
ferrichrome for the
ferrichrome-transport pathway in Streptococcus pneumoniae. R-825 inhibited the bacterial growth of S. pneumoniae and stimulated the expression of PiuA, the
iron-binding protein in the
ferrichrome-uptake system on the cell surface. R-825 treatment decreased the cellular content of
iron, accompanying with the increase of Ru(II) level in the bacterium. When the piuA gene (SPD_0915) was deleted in the bacterium, the mutant strain became resistant to R-825 treatment, with decreased content of Ru(II). Addition of
ferrichrome can rescue the bacterial growth that was suppressed by R-825. Fluorescence spectral quenching showed that R-825 can bind with PiuA in a similar pattern to the
ferrichrome-PiuA interaction in vitro. These observations demonstrated that Ru(II) complex R-825 can compete with
ferrichrome for the
ferrichrome-transport system to enter S. pneumoniae, reduce the cellular
iron supply, and thus suppress the bacterial growth. This finding suggests a novel antimicrobial approach by interfering with
iron-uptake pathways, which is different from the mechanisms used by current
antibiotics.