Microbial iron-binding proteins and iron-dependent enzymes

Microbial iron-binding proteins and iron-dependent enzymes are essential components of pathogen survival, facilitating the acquisition and utilization of iron, a vital nutrient that is strictly limited within the host environment [1.1.1, 1.5.1]. This target class includes siderophore receptors and transporters (e.g., FhuA, FpvA) that scavenge iron from host proteins like transferrin, as well as intracellular enzymes such as ribonucleotide reductase and cytochromes that require iron for DNA synthesis and energy production [1.2.2, 1.5.3]. Because pathogens rely on these systems to overcome host nutritional immunity, they are highly susceptible to strategies that either starve the microbe of iron or exploit uptake pathways for drug delivery [1.5.2, 1.5.4]. The most prominent clinical application is the Trojan horse antibiotic cefiderocol, which uses a siderophore-like moiety to bypass membrane barriers and deliver a beta-lactam payload directly to its target [1.3.1, 1.3.5]. Additionally, iron mimetics like gallium nitrate can disrupt bacterial metabolism by substituting for iron in redox-active enzymes, leading to metabolic arrest and increased sensitivity to oxidative stress [1.1.1, 1.1.4]. While promising for treating multidrug-resistant infections, therapeutic development must account for potential host toxicity and the ability of bacteria to adapt through mutations in iron transport machinery [1.2.1, 1.4.4].

Other names

Siderophore receptorsIron acquisition systemsMicrobial metalloenzymesFerric-binding proteinsBacterial iron transportersIron-sulfur cluster proteins

Trojan horse delivery of antibiotics via siderophore transport systems; competitive inhibition of iron-dependent enzymes by iron mimetics; sequestration of essential iron to induce nutritional starvation.