School Seminar: Prof Alastair McEwan, University of Queensland. “Copper and zinc ions as antibacterial agents – new opportunities using ionophores”
Professor Alastair McEwan, School of Chemistry and Molecular Biosciences, University of Queensland.
Host: A/Prof Liz New
Although zinc is an essential transition metal ion for all bacteria and in some species copper ions play an important role in enzymes associated with aerobic metabolism and in denitrification, in excess these metal ions are toxic. In this seminar I will describe the identification of key iron-sulfur cluster-containing enzymes as targets for copper toxicity, with a focus on the pathogen Neisseria gonorrhoeae. In the case of zinc we have observed that Group A Streptococcus (GAS) mutants that lack the czcD zinc efflux system are more susceptible to killing by this ion in vitro and by neutrophils, suggesting that zinc plays an antibacterial role in these innate immune cells. I will also describe some of the targets for zinc toxicity in GAS appear that are linked to central carbon metabolism. Exploiting the potential of zinc and copper as antimicrobials requires the development of metal ion coordination compounds that can overcome bacterial defense systems against zinc and copper toxicity. I will describe the use of metal ion ionophores to potentiate the toxicity of copper and zinc and our recent demonstration of the synergistic antimicrobial effects of zinc ionophores and antibiotics.