Metal imaging in Gram-negative bacteria: insights into mode of action of antibiotics

Understanding antibiotic resistance is of urgent need and a current global problem. We study the use of nitroxoline (Nx) as an antibiotic against multi-drug bacteria. Our recent results show that Nx treatment perturbs metal homeostasis in Gram-negative bacteria by acting as an ionophore that drags distinct metals inside the cell, which leads to metal intoxiciaction and subsequent cell death. Consistent with this model, iron, zinc and manganese are significantly elevated in Nx exposed E. coli cells. However, currently there is no information on the metal localization in Nx treated cells. We hypothesize that certain metals (especially Fe, Zn, Mn) are not evenly distributed but stored in specific regions as shown for other bacteria. To address this question, we would like to use X-ray fluorescence nano-imaging in E. coli under Nx treatment and control conditions. This approach will be crucial to reveal the metal accumulation within the cells and elucidate the mode of action of Nx.