Disentangling the Evolutionary History of Feo, the Major Ferrous Iron Transport System in Bacteria

Feo, a ferrous iron transport system composed of three proteins (FeoA, -B, and -C), is the most prevalent bacterial iron transporter. It plays an important role in iron acquisition in low-oxygen environments and some host-pathogen interactions.

Role of the processes of angiogenesis, proteolysis, iron transport and changes of morpho- functional status of immunocompetent cells in the pathogenesis of infiltrative endometriosis

The paper reports of the activation of the callikrein - kinine system, increased levels of vascular-endothelial growth factor, disturbances in the system of transport and exchange of iron and specific changes of morpho-functional status of immune- competent cells in peritoneal fluid in cases of infiltrative endometriosis, possibly responsible for aggressive course of this severe form of the disease and resistance to treatment.

Iron Transport and Metabolism in Escherichia, Shigella, and Salmonella

Iron is an essential element for Escherichia , Salmonella , and Shigella species. The acquisition of sufficient amounts of iron is difficult in many environments, including the intestinal tract, where these bacteria usually reside.

Staphylococcus aureus iron-regulated surface determinant B (IsdB) protein interacts with von Willebrand factor and promotes adherence to endothelial cells

Staphylococcus aureus is the cause of a spectrum of diseases in humans and animals. The molecular basis of this pathogenicity lies in the expression of a variety of virulence factors, including proteins that mediate adherence to the host plasma and extracellular matrix proteins. In this study, we discovered that the iron-regulated surface determinant B (IsdB) protein, besides being involved in iron transport and vitronectin binding, interacts with von Willebrand Factor (vWF). IsdB-expressing bacteria bound to both soluble and immobilized vWF. The binding of recombinant IsdB to vWF was blocked by heparin and reduced at high ionic strength. Furthermore, treatment with ristocetin, an allosteric agent that promotes the exposure of the A1 domain of vWF, potentiates the binding of IsdB to vWF. Both near-iron transporter motifs NEAT1 and NEAT2 of IsdB individually bound recombinant A1 domain with KD values in the micromolar range. The binding of IsdB and adhesion of S. aureus expressing IsdB to monolayers of activated endothelial cells was significantly inhibited by a monoclonal antibody against the A1 domain and by IsdB reactive IgG from patients with staphylococcal endocarditis. This suggests the importance of IsdB in adherence of S. aureus to the endothelium colonization and as potential therapeutic target.

TAMI-54. SEXUAL DIMORPHISM IN IRON ACQUISITION IN GLIOBLASTOMA

Sexual dimorphism in incidence and the clinical outcomes of Glioblastoma (GBM) has been reported, however, our knowledge of contributing biological mechanisms is limited. Iron acquisition is key to robust tumor growth. Upregulation of Transferrin (TF, iron transport protein)/Transferrin receptor (TFR) is critical for found in multiple different cancers, specifically, we have identified H-ferritin (FTH1) as a contributor to iron transport and protection in cancer stem cells. To interrogate brain tumor iron uptake mechanisms,we performed binding studies on homogenized samples of human male and female GBM tissue samples using 125I labeled TF and FTH1. Tumors from males had a ̴ 3.8-fold increased binding of both proteins compared to tumors from females. We interrogated iron uptake in a syngeneic orthotopic mouse model (GL261 cells) using male and female mice. After the tumors were established, radioactive 125I labeled TF and FTH1 proteins were injected retro-orbitally in the mice. After 24 hours, tumors wereremoved, and analyzed for TF and FTH1 uptake. Male tumors showed an increased uptake, of ̴ 3.2-fold, as compared to female tumors. There was no significant difference in TF uptake between male and female tumors nor between tumor and matched non-tumor brain tissue. We next queried role of FTH1 in the context of sexual dimorphism in GBM in a FTH1+/- mouse strain developed in our laboratory. Survival was monitored in the mice which were injected with GL261 cells at 3 months. Male mice that had reduced expression of FTH1 had poorer survival as compared to the male wild type controls whereas wild type and FTH+/- females had no major differences in survival outcomes. In summary, this study demonstrates sexual dimorphism in iron acquisition in GBM and animal models further suggesting a pathophysiological role of iron metabolism in GBM development and its possible role in prognosis.

Iron, Ferritin and Hepcidin Levels in Patients with Iron Deficiency Anemia

This study was conducted to identify the role of some blood parameters, levels of some hormones, proteins, and cellular kinetics that have a role in iron transport and storage, in addition to their relationship with each other and with blood and sex parameters for patients with severe and moderate iron deficiency anemia, and to compare the parameters with healthy people. The study period lasted for the period from (December 2020 until March 2021) The presence of iron deficiency anemia was confirmed by examining the blood picture and the criteria of hepcidin and ferritin. The results showed a significant decrease in the in the concentration of hepcidin, ferritin and iron in patients compared to the control group.

Staphylococcus Aureus Iron-Regulated Surface Determinant B (IsdB) Protein Interacts with von Willebrand Factor and Promotes Adherence to Endothelial Cells.

Staphylococcus aureus is the cause of a spectrum of diseases in humans and animals. The molecular basis of this pathogenicity lies in the expression of a variety of virulence factors, including proteins that mediate adherence to the host plasma and extracellular matrix proteins. In this study, we discovered that the iron-regulated surface determinant B (IsdB) protein, besides being involved in iron transport and vitronectin binding, interacts with von Willebrand Factor (vWF). IsdB-expressing bacteria bound to both soluble and immobilized vWF. The binding of recombinant IsdB to vWF was blocked by heparin and reduced at high ionic strength. Furthermore, treatment with ristocetin, an allosteric agent that promotes the exposure of the A1 domain of vWF, potentiates the binding of IsdB to vWF. Both near-iron transporter motifs NEAT1 and NEAT2 of IsdB individually bound recombinant A1 domain with KD values in the micromolar range. The binding of IsdB and adhesion of S. aureus expressing IsdB to monolayers of activated endothelial cells was significantly inhibited by a monoclonal antibody against the A1 domain and by IsdB reactive IgG from patients with staphylococcal endocarditis. This suggests the importance of IsdB in adherence of S. aureus to the endothelium colonization and as potential therapeutic target.

Impact of Human Serum Proteins on Susceptibility of Acinetobacter baumannii to Cefiderocol: role of iron transport

Cefiderocol is a siderophore antibiotic that co-opts iron transporters to facilitate cell entry. We show that genes related to iron uptake systems and resistance to β-lactams in Acinetobacter baumannii have altered expression levels in the presence of human serum, human serum albumin, or human pleural fluid. Cefiderocol MICs are also raised in the presence of the mentioned fluids. Clinical response in A. baumannii infections may be related to the interplay of these human factors.