Bacterial siderophore

Bacterial siderophores are low molecular weight, high-affinity iron-chelating molecules synthesized and secreted by many bacteria (and some fungi) to scavenge iron from their environment under conditions of iron limitation[1][2][3][4][6][8][10]. Siderophores bind Fe3+ with very high affinity—often exceeding host iron-binding proteins—and are critical for bacterial survival, virulence, and colonization in iron-poor environments such as the mammalian host[1][8][9]. After chelating iron, the siderophore–iron complex is recognized and imported by specific bacterial transporters (including TonB-dependent receptors and ABC transporters). Bacterial siderophores are chemically diverse and mainly grouped into the categories of catecholates (e.g., enterobactin, salmochelin), hydroxamates (e.g., desferrioxamine, ferrichrome), carboxylates (e.g., rhizobactin, staphyloferrin), and mixed types (e.g., yersiniabactin)[2][4][6][10]. Beyond iron acquisition, bacterial siderophores can play “non-classical” biological roles, such as acting as virulence factors, competing with the host’s defense proteins (e.g., siderocalin), functioning in the acquisition of other metals (zincophores, chalkophores), serving as signaling molecules, regulating oxidative stress, and possessing inherent antibiotic activity[7][8]. Siderophores are recognized as therapeutic targets because their biosynthesis, secretion, import, and iron-scavenging capabilities are essential for pathogenic bacteria during infection, and thus several drugs exploit siderophore-mediated transport (“Trojan horse” antibiotics) or act as chelators in iron overload diseases[10]. Deferoxamine is a clinically used iron chelator originally isolated as a microbial siderophore, and cefiderocol and similar molecules use siderophore groups for targeted drug delivery into bacteria. Their measurement in biological samples can serve as biomarkers of infection, and interfering with siderophore production or function is a promising antimicrobial strategy[3][4][10]. Note: “Bacterial siderophore” is a chemical system rather than a single molecular target such as a receptor or enzyme; in drug development, siderophore receptors or biosynthetic enzymes are usually the direct molecular targets, so this entry may be considered “incorrect” as a therapeutic target under strict criteria. However, drugs do interact with the siderophore system, making the bacterial siderophore pathway an established focus of antimicrobial research[10].

Other names

siderophoremicrobial siderophore

Iron chelation, Siderophore–drug conjugate uptake, Inhibition of iron uptake