Iron-loaded bacterial catecholate siderophores

Iron-loaded bacterial catecholate siderophores are high-affinity iron-chelating molecules, such as enterobactin, secreted by bacteria to scavenge ferric iron (Fe3+) from the host environment (PubMed, 2003). These molecules utilize catechol functional groups to form stable complexes with iron, which are then recognized and actively internalized by specific bacterial outer membrane transporters, such as TonB-dependent receptors (Nature, 2004). This process is essential for bacterial survival and virulence, as iron is a strictly limited nutrient within the human host. The human immune system counters this by producing Lipocalin-2 (also known as Siderocalin), which sequesters iron-loaded catecholates to starve the bacteria of iron (Cell, 2004). In drug development, this system is exploited through the Trojan Horse strategy, exemplified by the antibiotic cefiderocol, which uses a catecholate-like side chain to gain entry into multidrug-resistant Gram-negative bacteria (The Lancet Infectious Diseases, 2019). By mimicking the natural siderophore, these drugs bypass traditional resistance mechanisms like porin loss or efflux pump upregulation. This targeting strategy is particularly effective against pathogens like Pseudomonas aeruginosa and Acinetobacter baumannii.

Other names

Catecholate siderophoresFerri-catecholatesEnterobactin-like siderophoresCatechol-type siderophoresEnterobactin

Drugs utilizing this target employ a Trojan Horse strategy, where a siderophore-mimetic moiety binds iron and is actively transported into the bacterial periplasm via TonB-dependent transporters (e.g., CirA, Fiu), bypassing porin-mediated resistance (FDA, 2019; Nature Reviews Microbiology, 2021).