Month: September 2022

IRON DEFENSES. "One of the first lines of defense against bacterial infection is the withholding of nutrients to prevent bacterial outgrowth in a process termed nutritional immunity. The most significant form of nutritional immunity is the sequestration of nutrient iron. The vast majority of vertebrate iron is intracellular, sequestered within the iron storage protein ferritin or complexed within the porphyrin ring of heme as a cofactor of hemoglobin or myoglobin." https://lnkd.in/epJAeXg View in LinkedIn

RAISE THE DRAWBRIDGE. "In cases of systemic infection, the organism responds by lowering its total serum iron, so as to make the serotransferrin present less saturated with iron...The iron apparently moves into the storage tissues from the circulation, and furthermore, it is withheld from circulation by the reticuloendothelial system." This results in low serum iron, high unsaturated iron binding, and more active serotransferrins. https://lnkd.in/e9yjFnc View in LinkedIn

IRON MOAT. "Vertebrates are devoid of free iron, ensuring that all bacterial pathogens encounter a period of iron starvation upon entering their hosts. In keeping with this, bacterial pathogens have evolved to sense iron depletion as a marker of vertebrate tissue. This sensing typically involves transcriptional control mediated by the iron-dependent repressor known as Fur (ferric uptake regulator)." https://lnkd.in/epJAeXg View in LinkedIn

STARVE THE INVADER. "The aerobic environment and neutral pH of serum ensures that extracellular iron is insoluble and hence difficult to access by invading pathogens. This difficulty is enhanced by the serum protein transferrin, which binds iron with an association constant of approximately 10(36).Taken together, these factors ensure that the amount of free iron available to invading bacteria is vastly less than what is required to replicate and cause disease." https://lnkd.in/epJAeXg View in LinkedIn

RAPID FREE IRON SCAVENGING. "In a healthy individual iron is largely intracellular, sequestered within ferritin or as a cofactor of heme complexed to hemoglobin within erythrocytes. Any extracellular free iron is rapidly bound by circulating transferrin. Hemoglobin or heme that is released as a result of natural erythrocyte lysis is captured by haptoglobin and hemopexin, respectively. Taken together, these factors ensure that vertebrate tissue is virtually devoid of free iron." https://lnkd.in/epJAeXg View in LinkedIn

"TRANSFERRINS are iron-binding blood plasma glycoproteins that control the level of free iron in biological fluids. Transferrin glycoproteins bind iron tightly, but reversibly. Although iron bound to transferrin is less than 0.1% (4 mg) of total body iron, it forms the most vital iron pool with the highest rate of turnover (25 mg/24 h)." https://lnkd.in/ech9XqN View in LinkedIn

TRANSFERRIN DYNAMICS. "The iron-deficient transferrins will inhibit the growth of certain bacteria and fungi by making iron unavailable for bacterial metabolism. Such activity is abolished if the transferrin is saturated with iron. Overwhelming evidence is now available to indicate that the transferrins play an important role in mammalian host-defense mechanisms." https://lnkd.in/e9yjFnc View in LinkedIn

PATHOGENS NEED IRON. "Haemophilus influenzae is an obligate human commensal/pathogen. This haem autotroph must acquire haem from its host to sustain aerobic growth." This is common for many pathogens, bacterial, fungal or viral. This obligate need for iron has led to a range of iron acquisition strategies by the invasive pathogens, and creative iron sequestering responses by their hosts. https://lnkd.in/egknWXi View in LinkedIn

IRON WARFARE. "Bacterial pathogens can acquire iron through receptor-mediated recognition of transferrin, lactoferrin, hemopexin, hemoglobin, or hemoglobin–haptoglobin complexes. Alternatively, secreted siderophores can remove iron from transferrin, lactoferrin, or ferritin, whereupon siderophore–iron complexes are recognized by cognate receptors at the bacterial surface." https://lnkd.in/epJAeXg View in LinkedIn

IRON ACQUISITION AND VIRULENCE. "Many organisms can produce small molecular-weight iron-binding compounds called siderophores that can successfully utilize the iron sequestered by the transferrins. Such organisms are very virulent." https://lnkd.in/e9yjFnc View in LinkedIn