Metal ions are essential for all living organisms. Finally, for metal-based antifungal compounds, we refer to the recent review by Lin et al. A significant body of research has been published on the use of nanoparticles as antimicrobial agents and has been reviewed elsewhere 19, 20. The use of metal complexes as adjuvants or potentiators, in combination with antibiotics or other biologically active compounds, is another fertile field of research, but beyond the scope of this Review. A comprehensive look at the molecular and cellular targets of metal ions was published by Lemire et al. 17 recently reviewed bioinorganic strategies against bacteria. This Review does not include a comprehensive list of all metalloantibiotics: interested readers are referred to excellent reviews that have been published on this topic 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16. We conclude by discussing the use of complexes of radioactive metal isotopes to improve the diagnosis of bacterial infections by visualizing their location, in a similar fashion to the detection of cancer through imaging. The Review includes a brief overview of the application of light-activated metal compounds against bacteria as an example of alternative mechanism of action that are possible with metalloantibiotics. We focus on antibacterial metal complexes and present examples for which the mechanism of action has been (at least partially) elucidated. We discuss the role of metal ions in bacteria and the potential of some metal ions to directly kill bacterial pathogens, along with strategies to hijack bacterial metal-ion pathways for antimicrobial activity. This Review covers the current state of metals and metalloantibiotics as antibacterial agents. However, only recently have metals and metalloantibiotics gained considerable attention as potential antimicrobials, in response to the rapid rise of AMR in the past decade. Since then, many metal-containing compounds have been studied for the treatment of diseases, with several entering human clinical trials 5. The discovery and regulatory approval of the anticancer drug cisplatin heralded the modern era of medicinal inorganic chemistry. Inorganic compounds, organometallic compounds, and/or metal complexes have had a small but seminal role in twentieth-century medicine. Hence, new approaches for developing the next generation of antibiotics are urgently needed. Despite this urgency, conventional organic medicinal chemistry has failed to replenish the depleted antimicrobial pipeline: a 2022 analysis showed that, as of June 2021, there were only 45 ‘traditional’ antibiotics in clinical development 4. This number is expected to reach 10 million deaths per year worldwide by 2050 2, if not sooner due in part to the widespread over-prescription of antibiotics to COVID-19 patients over the past 2 years 3.

In 2019, there were an estimated 4.95 million deaths associated with AMR, of which 1.3 million were directly attributable to resistant infections 1. We also provide an overview of alternative uses of metal complexes to combat bacterial infections, including antimicrobial photodynamic therapy and radionuclide diagnosis of bacterial infections.Īntimicrobial resistance (AMR) is on track to become the leading cause of death of world in the coming decades. This Review summarizes recent developments in this growing field, focusing on advances in the development of metalloantibiotics, in particular, those for which the mechanism of action has been investigated. Although yet to be advanced to the clinic, metalloantibiotics are a vast and underexplored group of compounds that could lead to a much-needed new class of antibiotics. The search for antibacterial agents now encompasses metal ions, nanoparticles and metal complexes with antimicrobial activity (‘metalloantibiotics’). Metal ions have a long history of antimicrobial activity and have received increasing attention in recent years owing to the rise of antimicrobial resistance. Bacteria, similar to most organisms, have a love–hate relationship with metals: a specific metal may be essential for survival yet toxic in certain forms and concentrations.

Cobalt electron configuration spy