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Metal complexes with bacterial activity

The research in this project has been aimed at defeating bacterial growth and subsequent infection of medical devices and biomaterials through the use of bioactive metal complexes. We set out to create long term stable polymer films that would coat medical devices and release therapeutic concentrations of antibacterial agents such as silver (Ag). The aim was to create antibacterial surfaces that allowed mammalian cells to grow and differentiate normally in the vicinity of the surface. The surfaces were extensively tested using bacterial and mammalian cells.

In our research we found that although silver is a very efficient antibacterial agent, it can also be harmful to mammalian cells, thus, making it less suitable as an antibacterial agent in medical devices. We found that in the presence of substances that can complex silver ions (such as serum proteins), the silver ions lose their cytotoxicity as well as their antibacterial effect. Thereby our results illustrate the importance of good experimental design for relevant testing of these types of surfaces, and that similar biological conditions need to be used when comparing cytotoxicity and antibacterial effects.

The continuation of the project has focused on other types of antibacterial agents in solution, for example gallium complexes and has shown that by altering the ligand to which gallium ions bind, the biological effect is changed.

This start of this project was co-founded by the Swedish Research Council, the Swedish Foundation for Strategic Research, VINNOVA and Curth Nilsons stiftelse för vetenskaplig forskning within a framework called “Biomedical Engineering for Improved Health” (Medicinsk teknik för bättre hälsa). The continuation was funded from the Swedish Research Council, the Kempe Foundation (instruments), and Umeå University.

Publications of interest:

2009, Bacterial and Mammalian Cell Response to Poly (3-Sulfopropyl methacrylate) Brushes Loaded with Silver Halide Salts

2011, Ligand complexation affects uptake and antibacterial effect of gallium in bacteria

2014, The gallium(III)–salicylidene acylhydrazide complex shows synergistic anti-biofilm effect and inhibits toxin production by Pseudomonas aeruginosa

2014, Proton and Gallium(III) Binding Properties of a Biologically Active Salicylidene Acylhydrazide

2016, Influence of Chelation Strength and Bacterial Uptake of Gallium Salicylidene Acylhydrazide on Biofilm Formation and Virulence by Pseudomonas aeruginosa