Microbial cellular metal homeostasis and iron–sulfur cluster enzymes

Microbial cellular metal homeostasis and iron–sulfur (Fe-S) cluster enzymes constitute a fundamental network required for the survival and virulence of bacterial and fungal pathogens (Hood & Skaar, 2012, Nature Reviews Microbiology). These systems manage the acquisition, trafficking, and incorporation of essential metal ions into proteins, where they serve as critical catalytic and structural cofactors (Braymer & Giedroc, 2014, Current Opinion in Chemical Biology). Fe-S clusters are particularly vital for electron transport, DNA repair, and metabolic regulation, with their assembly being mediated by specialized machineries such as the ISC (iron-sulfur cluster) and SUF (sulfur mobilization) systems (Ezraty et al., 2017, Nature Reviews Molecular Cell Biology). Because these pathways are essential and often differ significantly from their eukaryotic counterparts, they are increasingly viewed as viable targets for antimicrobial therapy (Bonneau et al., 2020, Trends in Microbiology). Therapeutic strategies include the use of metal mimetics like gallium, which disrupts iron-dependent metabolism, and the development of small molecules that inhibit Fe-S cluster biogenesis or the regulatory proteins that sense metal levels (Richter et al., 2017, Frontiers in Cellular and Infection Microbiology).

Other names

Microbial metal metabolismFe-S cluster biogenesis and maintenanceMicrobial metallostasisBacterial iron-sulfur cluster assembly systems

Disruption of iron-sulfur cluster assembly, competitive inhibition of iron uptake, and induction of oxidative stress through metal imbalance.