Effects of Desferrioxamine-gallium compounds on bacteria

Over 70% of nosocomial infections in the United States are resistant to one or more traditional antibiotics; yet there continues to be an insufficient variety of treatments.  In the United States alone, bacterial infections caused by methicillin-resistant Staphylococcus aureus (MRSA) contribute to 90,000 deaths annually.  Metal ions are theorized to render bacterial cells non-viable by three different methods: breaking the bacterium cell wall, inhibiting vital enzymatic functioning, or directly attacking the bacterium DNA.  Due to the variety of mechanisms with which metal ions attack bacteria and the current lack of significant resistance to these metal-based methods, these treatments are an attractive alternative to traditional antibiotics.  Our study aims to chelate gallium (Ga) onto siderophore compounds, specifically desferrioxamine (DFO), in order to effectively treat resistant bacteria.  Once synthesized, the DFO-Ga complex will be tested against Corynebacterium xerosis, Mycobacterium smegmatis, Alcaligenes faecalis, Enterobacter aerogenes, Staphylococcus aureus, and Staphylococcus epidermidis as model strains for siderophore piracy to determine the specificity of siderophore uptake.  This “Trojan Horse” method is hypothesized to be more effective in evading the development of new resistance in the treatment of strains of resistant pathogens.  Our research aims to prove the feasibility of siderophore piracy, a mechanism that allows for the uptake of iron into bacterial cultures through secondary means, to enable more cost efficient and readily producible alternative treatment routes.  In showing the feasibility of siderophore piracy mechanisms, our research will enable the development of future avenues of protecting against resistant nosocomial infections.