Bacterial iron metabolism and iron-dependent enzymes

Bacterial iron metabolism and iron-dependent enzymes encompass the machinery used by bacteria to acquire, transport, and utilize iron, which is essential for DNA synthesis, respiration, and metabolic catalysis (Andrews et al., 2003). Because the human host actively sequesters iron to limit bacterial growth—a defense known as nutritional immunity—pathogens rely on high-affinity siderophores and specialized transporters to scavenge iron from host proteins like transferrin (Hood & Skaar, 2012). These pathways are highly attractive for antimicrobial development, particularly through the use of siderophore-drug conjugates like Cefiderocol, which exploit bacterial iron transporters to deliver antibiotics directly into the cell (Zhanel et al., 2019). Additionally, iron mimetics such as gallium can disrupt iron-dependent enzymatic functions by substituting for iron in proteins like ribonucleotide reductase, effectively starving the bacteria of a functional cofactor (Goss et al., 2018). Targeting these systems provides a strategy to overcome multi-drug resistance by utilizing the bacteria's own essential nutrient acquisition pathways. This approach is particularly relevant for Gram-negative pathogens where the outer membrane presents a significant barrier to traditional antibiotics.

Other names

Bacterial iron acquisition systemsSiderophore-mediated iron uptakeBacterial iron homeostasisHeme acquisition systemsNutritional immunity targets

Siderophore-mediated active transport (Trojan horse) and iron mimetic substitution (Zhanel et al., 2019; Goss et al., 2018).