Role of Iron in Bacterial Pathogenesis: Clinical Takeaways from an Editorial Original paper

What was reviewed?

This editorial synthesizes evidence on the role of iron in bacterial pathogenesis, emphasizing how iron scarcity and host nutritional immunity shape virulence, metabolic strategy, and antibiotic tolerance across diverse pathogens. Mechanisms covered include siderophore production and piracy, heme acquisition, ferrous iron uptake via Feo, and regulatory circuitry such as Fur and the newly identified ExrR. Therapeutic concepts such as heme analog antimetabolites are highlighted alongside host responses that restrict iron bioavailability. The focus is translational, linking molecular iron handling to clinical outcomes and potential interventions relevant to the role of iron in bacterial pathogenesis.

Who was reviewed?

The editorial curates contributions spanning extracellular and intracellular pathogens and multiple host contexts. Examples include Yersinia pestis toggling between yersiniabactin and Feo according to oxygen tension, fish pathogens Vibrio anguillarum and Photobacterium damselae, the Burkholderia cepacia complex in cystic fibrosis, Francisella tularensis with TonB-independent rhizoferrin uptake, and FupA-mediated Fe²⁺ transport. Regarding the role of iron in bacterial pathogenesis, Pseudomonas aeruginosa targeted by gallium–protoporphyrin IX, Ehrlichia ruminantium with ExrR-linked T4SS induction under iron depletion, Riemerella anatipestifer with Fur-dependent virulence, Mycobacterium tuberculosis exploiting surface GAPDH to bind host lactoferrin, and Salmonella Typhimurium where hepcidin-driven hypoferremia and iron overload modulate bacterial burden in vivo.

Most important findings

Across taxa, iron limitation is a cue that upregulates iron-acquisition systems and virulence programs. Pathogens flexibly switch among siderophores, xenosiderophore uptake, heme receptors, and Feo transport depending on oxygen, pH, and niche, which highlights how the role of iron in bacterial pathogenesis varies. Host nutritional immunity responds with hemopexin, transferrin, and hepcidin to curtail extracellular and dietary iron, yet pathogens often co-opt these same host proteins. Clinically relevant signals emerge: genetic or dietary iron overload increases susceptibility, lactoferrin can become an inadvertent iron source for M. tuberculosis via GAPDH, and heme analogs such as GaPPX can pharmacologically exploit bacterial heme receptors. Iron storage proteins (bacterioferritin and ferritin) may intersect with drug resistance networks, nominating novel targets like Rv1877.

Key implications

For clinicians, iron status is integral to infectious risk and therapeutic planning. Avoid unnecessary iron enrichment during active infection or in iron-overload phenotypes given evidence that excess iron augments pathogen biomass. Consider host-directed strategies that modulate hepcidin or leverage lactoferrin while recognizing that certain pathogens directly exploit these proteins. Notably, the role of iron in bacterial pathogenesis can guide pathogen-directed opportunities, including blocking siderophore systems, inhibiting Feo transport in microaerobic niches, and targeting heme receptors with analogs like GaPPX. From a microbiome-signatures perspective, iron tension is a cross-cutting ecological driver that selects for organisms with efficient iron piracy; mapping siderophore families, heme receptor repertoires, and Feo presence can refine microbial associations tied to iron-rich or iron-restricted niches. Iron storage and regulatory proteins intersect with antimicrobial resistance, suggesting combinatorial regimens that pair conventional antibiotics with iron-pathway disruptors.

Citation

Zughaier SM, Cornelis P. Editorial: Role of Iron in Bacterial Pathogenesis. Frontiers in Cellular and Infection Microbiology. 2018;8:344. doi:10.3389/fcimb.2018.00344.