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

Understanding antimicrobial resistance in bacteria is mandatory to develop new antibiotic therapies. We could show that the anti-infective nitroxoline (Nx) is active against multidrug-resistant bacteria. Nx acts as an ionophore by transporting metals into the bacterial cell, but the mode of action remain largely unknown. Our previous results indicate increase of Mn, Zn and Fe upon Nx treatment as well as Cu accumulation in the periplasm, suggesting perturbation of metal homeostasis by Nx. Furthermore, X-ray fluorescence (XRF) imaging indicates storage of Fe in clusters in untreated E. coli cells. Storage of metals in highly organized intracellular compartments is known to provide resistance against metal stress [1]. We hypothesize that Nx disrupts organization of metal clusters and apply for 2D and 3D XRF nano-imaging to decipher mode of action and resistance mechanism by analyzing Nx-susceptible and resistance generated E. coli cells.