CO-releasing Metal Carbonyl Compounds as Antimicrobial Agents in the Post-antibiotic Era

Abstract

The possibility of a "post-antibiotic era" in the 21st century, in which common infections may kill, has prompted research into radically new antimicrobials. CO-releasing molecules (CORMs), mostly metal carbonyl compounds, originally developed for therapeutic CO delivery in animals, are potent antimicrobial agents. Certain CORMs inhibit growth and respiration, reduce viability, and release CO to intracellular hemes, as predicted, but their actions are more complex, as revealed by transcriptomic datasets and modeling. Progress is hindered by difficulties in detecting CO release intracellularly, limited understanding of the biological chemistry of CO reactions with non-heme targets, and the cytotoxicity of some CORMs to mammalian cells.

Keywords: antibiotic resistance; antimicrobial agents; bacterial metabolism; carbon monoxide; heme; heme oxygenase; metal carbonyl compound; metal homeostasis; respiratory chain; transport metal.