Tackling microbial iron homeostasis: novel antimicrobial strategies
Alexander Hoffmann, Philipp Grubwieser, Dirk Bumann, David Haschka, Günter Weiß
Abstract
The escalating threat of antimicrobial resistance demands innovative therapeutic strategies beyond classical targets. Recent insights into the mechanisms of bacterial iron acquisition - ranging from siderophores and heme uptake to ferrous iron transport - have enabled new approaches to impair pathogen growth and virulence. These pathways are increasingly being harnessed for therapeutic gain. Emerging strategies include next-generation iron chelators with improved specificity and reduced toxicity, gallium-based iron mimics that disrupt redox metabolism, and siderophore-drug conjugates that hijack bacterial uptake systems for targeted delivery. In parallel, antivirulence agents such as hemolysin inhibitors are promising resistance-sparing alternatives by targeting iron-driven pathogenesis. In this review we highlight these advances and emphasize the potential of host-mediated iron sequestration and bio-inspired nanotechnologies to strengthen nutritional immunity and guide future antimicrobial strategies.