Microbial iron sequestration pathway

The microbial iron sequestration pathway comprises a suite of strategies evolved by bacteria and fungi to acquire iron, an essential element for growth and metabolism, from otherwise iron-limited environments such as during host infection. The pathway most prominently involves the synthesis and secretion of siderophores—small, high-affinity iron-chelating molecules—that bind environmental Fe(III) and are then actively transported back into the microbial cell via specific outer membrane receptors and ABC transporter systems[2][4][5]. Some pathogens may also directly extract iron from host proteins (transferrin, lactoferrin, hemoglobin) using dedicated membrane receptors[3][4]. This pathway is a prominent driver of microbial virulence and a major battlefield in host-pathogen interactions, as the host also actively sequesters iron to limit pathogen growth (nutritional immunity)[4][6]. Drugs such as cefiderocol exploit siderophore uptake systems to achieve efficient delivery into bacteria, establishing components of this pathway as validated or promising targets in infectious disease pharmacology[4][5]. In summary, as formulated, "Microbial iron sequestration pathway" designates a biological process consisting of many potential molecular targets, rather than a single molecular target. For structured target annotation, it should be refined to individual molecules such as "FepA (siderophore receptor)" or "FeoB (ferrous iron transporter)" for higher specificity and actionable drug discovery relevance.

Other names

Siderophore-mediated iron uptakeSiderophore pathwayBacterial iron acquisition pathwayMicrobial iron uptake system

Trojan horse strategy: antibiotics or molecules (e.g., cefiderocol) are conjugated to siderophores, enabling active uptake through microbial iron transporters and subsequent antibacterial action inside the cell. Inhibition/blockade of siderophore receptors or iron transporter function (prevents iron acquisition, reducing microbial survival). Chelation of extracellular iron to compete with microbial uptake.