The threat of bacterial resistance to antibiotics requires new approaches in antimicrobial development. The use of metal and metalloid complexes to treat bacterial infection is not novel, as these were extensively used before the rise of antibiotics in the 1940s.
Metal complexes that were once considered as anticancer compounds are currently being investigated for their potential as antimicrobials. Past studies under the supervision of Associate Professor Jeff Warner into metal based agents, particularly compounds incorporating ruthenium complexes show promise with low inhibitory and bactericidal concentrations, while maintaining low toxicity in eukaryotic cell lines. However, these complexes in in vivo studies show poor tolerability in murine models.
Recent studies into synthetic ligands with lanthanide show potential as future antimicrobials with toxicity concentrations significantly higher than the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Curiously, certain ruthenium and lanthanide compounds feature preferential activity against Gram negative bacteria such as Escherichia coli and Pseudomonas aeruginosa, which may suggest inhibitory mechanisms that are unaffected by membrane bound active efflux pumps; a key antimicrobial resistance feature of P. aeruginosa. The objective of this proposed study is to investigate the lanthanide compounds as potential antimicrobials in regards to their in vitro efficacy against pathogens and in vivo tolerability and kinetics in a murine model.
The Aim of your project is to:
Supervisor: A/Prof Jeffrey Warner