Metal–Ligand Interactions: Overlooked Confounders in Antibiotic Discovery and Development

The unabating rise of antimicrobial resistance makes the development of novel and effective antibiotics an urgent global health need. Progress toward assuaging this need is, however, limited by low levels of investment and patently low financial incentives. Eliminating inefficiencies in antibiotic development is therefore important to ensure effective deployment of limited resources. Metal interference in high-throughput assays, mechanism of action studies, and the eventual pharmacokinetics of antibiotics in development is an overlooked confounder in this process. In this Viewpoint, we, focusing on antibiotics, briefly provide a compartment-based approach to anticipating various possibilities for such interference and recommend toolkits for identification.