Tackling microbial iron homeostasis: novel antimicrobial strategies.

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.