Iron Sequestration Research Articles

Non-classical roles of bacterial siderophores in pathogenesis.

Within host environments, iron availability is limited, which instigates competition for this essential trace element. In response, bacteria produce siderophores, secondary metabolites that scavenge iron and deliver it to bacterial cells via specific receptors. This role in iron acquisition contributes significantly to bacterial pathogenesis, thereby designating siderophores as virulence factors. While prior research has primarily focused on unravelling the molecular mechanisms underlying siderophore biosynthesis, uptake, and iron sequestration, recent investigations have unveiled additional non-iron chelating functions of siderophores. These emerging roles are being consistently shown to support bacterial pathogenesis. In this review, we present the current understanding of siderophores in various roles: acquiring non-iron metal ions, supporting tolerance to metal-induced and reactive oxygen species (ROS)-induced stresses, mediating siderophore signalling, inducing ROS formation, and functioning in class IIb microcins. By integrating recent findings, this review aims to provide an overview of the diverse roles of siderophores in bacterial pathogenesis.

Quinoline-based tetrazolium prochelators: formazan release, iron sequestration, and antiproliferative efficacy in cancer cells.

Iron-binding strategies in anticancer drug design target the key role of iron in cancer growth. The incorporation of a quinoline moiety in the design of tetrazolium-based prochelators facilitates their intracellular reduction/activation to iron-binding formazans. The new prochelators are antiproliferative at submicromolar levels, induce apoptosis and cell cycle arrest, and impact iron signaling in cancer cells.

Total substitution and partial modification of the set of non-ribosomal peptide synthetases clusters lead to pyoverdine diversity in the Pseudomonas fluorescens complex.

Pyoverdines are high affinity siderophores produced by most Pseudomonas with a wide role in microbial interspecies interactions. They are primarily composed of a conserved chromophore moiety, an acyl side chain and a peptide backbone which may be highly variable among strains. Upon ferric iron sequestration, pyoverdines are internalized through specialized receptors. The peptide precursor of pyoverdine, termed ferribactin, is synthesized by a set of non-ribosomal peptide synthetase (NRPS) enzymes and further modified by tailoring enzymes. While PvdL, the NRPS responsible for the synthesis of the peptide moiety that derives into the chromophore is conserved, the NRPSs for the peptide backbone are different across fluorescent Pseudomonas. Although the variation of pyoverdine is a widely recognized characteristic within the genus, the evolutionary events associated with the diversity and distribution of this trait remain mostly unknown. This study analyzed the NRPSs clusters for the biosynthesis of the peptide backbone of ferribactin in the genomes of a representative subset of strains of the Pseudomonas fluorescens complex. Bioinformatic analysis of the specificity of adenylation domains of the NRPSs allowed the prediction of 30 different pyoverdine variants. Phylogenetic reconstruction and mapping of the NRPS clusters pinpointed two different general levels of modifications. In the first level, a complete replacement of the set of NRPRs by horizontal transfer occurs. In the second level, the original set of NRPSs is modified through different mechanisms, including partial substitution of the NRPS genes by horizontal transfer, adenylation domain specificity change or NRPS accessory domain gain/loss.

Nutritional Modulation of Hepcidin in the Treatment of Various Anemic States.

Twenty years after its discovery, hepcidin is still considered the main regulator of iron homeostasis in humans. The increase in hepcidin expression drastically blocks the flow of iron, which can come from one's diet, from iron stores, and from erythrophagocytosis. Many anemic conditions are caused by non-physiologic increases in hepcidin. The sequestration of iron in the intestine and in other tissues poses worrying premises in view of discoveries about the mechanisms of ferroptosis. The nutritional treatment of these anemic states cannot ignore the nutritional modulation of hepcidin, in addition to the bioavailability of iron. This work aims to describe and summarize the few findings about the role of hepcidin in anemic diseases and ferroptosis, as well as the modulation of hepcidin levels by diet and nutrients.

Protein Phosphorylation Orchestrates Acclimations of Arabidopsis Plants to Environmental pH

Environment pH (pHe) is a key parameter dictating a surfeit of conditions critical to plant survival and fitness. To elucidate the mechanisms that recalibrate cytoplasmic and apoplastic pH homeostasis, we conducted a comprehensive proteomic/phosphoproteomic inventory of plants subjected to transient exposure to acidic or alkaline pH, an approach that covered the majority of protein-coding genes of the reference plant Arabidopsis thaliana. Our survey revealed a large set-of so far undocumented pHe-dependent phospho-sites, indicative of extensive post-translational regulation of proteins involved in the acclimation to pHe. Changes in pHe altered both electrogenic H+ pumping via P-type ATPases and H+/anion co-transport processes, putatively leading to altered net trans-plasma membrane translocation of H+ ions. In pH 7.5 plants, the transport (but not the assimilation) of nitrogen via NRT2-type nitrate and AMT1-type ammonium transporters was induced, conceivably to increase the cytosolic H+ concentration. Exposure to both acidic and alkaline pH resulted in a marked repression of primary root elongation. No such cessation was observed in nrt2.1 mutants. Alkaline pH decreased the number of root hairs in the wild type but not in nrt2.1 plants, supporting a role of NRT2.1 in developmental signaling. Sequestration of iron into the vacuole via alterations in protein abundance of the vacuolar iron transporter VTL5 was inversely regulated in response to high and low pHe, presumptively in anticipation of associated changes in iron availability. A pH-dependent phospho-switch was also observed for the ABC transporter PDR7, suggesting changes in activity and, possibly, substrate specificity. Unexpectedly, the effect of pHe was not restricted to roots and provoked pronounced changes in the shoot proteome. In both roots and shoots, the plant-specific TPLATE complex components AtEH1 and AtEH2-essential for clathrin-mediated endocytosis-were differentially phosphorylated at multiple sites in response to pHe, indicating that the endocytic cargo protein trafficking is orchestrated by pHe.

Examining the Role of a Functional Deficiency of Iron in Lysosomal Storage Disorders with Translational Relevance to Alzheimer's Disease.

The recently presented Azalea Hypothesis for Alzheimer's disease asserts that iron becomes sequestered, leading to a functional iron deficiency that contributes to neurodegeneration. Iron sequestration can occur by iron being bound to protein aggregates, such as amyloid β and tau, iron-rich structures not undergoing recycling (e.g., due to disrupted ferritinophagy and impaired mitophagy), and diminished delivery of iron from the lysosome to the cytosol. Reduced iron availability for biochemical reactions causes cells to respond to acquire additional iron, resulting in an elevation in the total iron level within affected brain regions. As the amount of unavailable iron increases, the level of available iron decreases until eventually it is unable to meet cellular demands, which leads to a functional iron deficiency. Normally, the lysosome plays an integral role in cellular iron homeostasis by facilitating both the delivery of iron to the cytosol (e.g., after endocytosis of the iron-transferrin-transferrin receptor complex) and the cellular recycling of iron. During a lysosomal storage disorder, an enzyme deficiency causes undigested substrates to accumulate, causing a sequelae of pathogenic events that may include cellular iron dyshomeostasis. Thus, a functional deficiency of iron may be a pathogenic mechanism occurring within several lysosomal storage diseases and Alzheimer's disease.

Genomic and microbiological analyses of iron acquisition pathways among respiratory and environmental nontuberculous mycobacteria from Hawai'i.

As environmental opportunistic pathogens, nontuberculous mycobacteria (NTM) can cause severe and difficult to treat pulmonary disease. In the United States, Hawai'i has the highest prevalence of infection. Rapid growing mycobacteria (RGM) such as Mycobacterium abscessus and M. porcinum and the slow growing mycobacteria (SGM) including M. intracellulare subspecies chimaera are common environmental NTM species and subspecies in Hawai'i. Although iron acquisition is an essential process of many microorganisms, iron acquisition via siderophores among the NTM is not well-characterized. In this study, we apply genomic and microbiological methodologies to better understand iron acquisition via siderophores for environmental and respiratory isolates of M. abscessus, M. porcinum, and M. intracellulare subspecies chimaera from Hawai'i. Siderophore synthesis and transport genes, including mycobactin (mbt), mmpL/S, and esx-3 were compared among 47 reference isolates, 29 respiratory isolates, and 23 environmental Hawai'i isolates. Among all reference isolates examined, respiratory isolates showed significantly more siderophore pertinent genes compared to environmental isolates. Among the Hawai'i isolates, RGM M. abscessus and M. porcinum had significantly less esx-3 and mbt genes compared to SGM M. chimaera when stratified by growth classification. However, no significant differences were observed between the species when grown on low iron culture agar or siderophore production by the chrome azurol S (CAS) assay in vitro. These results indicate the complex mechanisms involved in iron sequestration and siderophore activity among diverse NTM species.

Seasonal and fasting induced changes in iron metabolism in Djungarian hamsters

Djungarian hamsters are small rodents that show pronounced physiological acclimations in response to changes in photoperiod, and unfavorable environmental conditions such as reduced food availability and low external temperature. These include substantial adjustments, such as severe body weight loss and the use of daily torpor. Torpor is a state of decreased physiological activity in eutherms, usually marked by low metabolic rate and a reduced body temperature. In this study, we investigated the effects of photoperiodic acclimation and food deprivation on systemic iron metabolism in Djungarian hamsters. Our study illustrates the association between liver iron levels and the incidence of torpor expression during the course of the experiment. Moreover, we show that both, acclimation to short photoperiods and long-term food restriction, associated with iron sequestration in the liver. This effect was accompanied with hypoferremia and mild reduction in the expression of principal iron-hormone, hepcidin. In addition to iron, the levels of manganese, selenium, and zinc were increased in the liver of hamsters under food restriction. These findings may be important factors for regulating physiological processes in hamsters, since iron and other trace elements are essential for many metabolic and physiological processes.

Two distinct non-ribosomal peptide synthetase-independent siderophore synthetase gene clusters identified in Armillaria and other species in the Physalacriaceae.

Siderophores are important for ferric iron solubilization, sequestration, transportation, and storage, especially under iron-limiting conditions such as aerobic conditions at high pH. Siderophores are mainly produced by non-ribosomal peptide synthetase-dependent siderophore pathway, non-ribosomal peptide synthetase-independent siderophore synthetase pathway, or the hybrid non-ribosomal peptide synthetases/non-ribosomal peptide synthetases-independent siderophore pathway. Outcompeting or inhibition of plant pathogens, alteration of host defense mechanisms, and alteration of plant-fungal interactions have been associated with fungal siderophores. To understand these mechanisms in fungi, studies have been conducted on siderophore biosynthesis by ascomycetes with limited focus on the basidiomycetes. Armillaria includes several species that are pathogens of woody plants and trees important to agriculture, horticulture, and forestry. The aim of this study was to investigate the presence of non-ribosomal peptide synthetases-independent siderophore synthetase gene cluster(s) in genomes of Armillaria species using a comparative genomics approach. Iron-dependent growth and siderophore biosynthesis in strains of selected Armillaria spp. were also evaluated in vitro. Two distinct non-ribosomal peptide synthetases-independent siderophore synthetase gene clusters were identified in all the genomes. All non-ribosomal peptide synthetases-independent siderophore synthetase genes identified putatively encode Type A' non-ribosomal peptide synthetases-independent siderophore synthetases, most of which have IucA_IucC and FhuF-like transporter domains at their N- and C-terminals, respectively. The effect of iron on culture growth varied among the strains studied. Bioassays using the CAS assay on selected Armillaria spp. revealed in vitro siderophore biosynthesis by all strains irrespective of added FeCl3 concentration. This study highlights some of the tools that Armillaria species allocate to iron homeostasis. The information generated from this study may in future aid in developing molecular based methods to control these phytopathogens.

Comparative pangenomic analysis of predominant human vaginal lactobacilli strains towards population-specific adaptation: understanding the role in sustaining a balanced and healthy vaginal microenvironment

The vaginal microenvironment of healthy women has a predominance of Lactobacillus crispatus, L. iners, L. gasseri, and L. jensenii. The genomic repertoire of the strains of each of the species associated with the key attributes thereby regulating a healthy vaginal environment needs a substantial understanding.We studied all available human strains of the four lactobacilli across different countries, isolated from vaginal and urinal sources through phylogenetic and pangenomic approaches. The findings showed that L. iners has the highest retention of core genes, and L. crispatus has more gene gain in the evolutionary stratum. Interestingly, L. gasseri and L. jensenii demonstrated major population-specific gene-cluster gain/loss associated with bacteriocin synthesis, iron chelating, adherence, zinc and ATP binding proteins, and hydrolase activity. Gene ontology enrichment analysis revealed that L. crispatus strains showed greater enrichment of functions related to plasma membrane integrity, biosurfactant, hydrogen peroxide synthesis, and iron sequestration as an ancestral derived core function, while bacteriocin and organic acid biosynthesis are strain-specific accessory enriched functions. L. jensenii showed greater enrichment of functions related to adherence, aggregation, and exopolysaccharide synthesis. Notably, the key functionalities are heterogeneously enriched in some specific strains of L. iners and L. gasseri.This study shed light on the genomic features and their variability that provides advantageous attributes to predominant vaginal Lactobacillus species maintaining vaginal homeostasis. These findings evoke the need to consider region-specific candidate strains of Lactobacillus to formulate prophylactic measures against vaginal dysbiosis for women’s health.

Phase transformation of nanoscale zero-valent iron and concurrent arsenite sequestration under oxic water environment

Nanoscale zero-valent iron (nZVI) may partially or completely transform to iron (hydr)oxides when it is used to remove arsenite [As(Ⅲ)]. It is necessary to explore the dynamic phase transformation of nZVI and concurrent arsenic valent changes since reactivity is relevant to the exiting species. In this study, X-ray photoelectron spectra (XPS), X-ray diffraction (XRD), Raman spectrum, and scanning electron microscope (SEM) were used to probe the phase transformation of nZVI under the varied simulated polluted water, including different As(Ⅲ) concentration, pH, and co-existing anions. The mainly final product of nZVI corrosion was lepidocrocite (γ-FeOOH) evaluated by XRD. Because of proton release, As(Ⅲ) made more Fe0 corroded in the initial reaction and the corrosion process was faster in the later stage. The formation of iron (hydr)oxides was the main factor affecting the removal of As(Ⅲ) between pH 2–8. And the co-existing anions promoted the corrosion of Fe0, which weakened the negative effect of competitive adsorption on As(Ⅲ) removal to some extent. This research will provide vital information on the evolution and fate of nZVI under environmental conditions, as well as As(Ⅲ) stabilization and mobilization for nZVI treatment system.

Why Is Iron Deficiency/Anemia Linked to Alzheimer's Disease and Its Comorbidities, and How Is It Prevented?

Impaired iron metabolism has been increasingly observed in many diseases, but a deeper, mechanistic understanding of the cellular impact of altered iron metabolism is still lacking. In addition, deficits in neuronal energy metabolism due to reduced glucose import were described for Alzheimer's disease (AD) and its comorbidities like obesity, depression, cardiovascular disease, and type 2 diabetes mellitus. The aim of this review is to present the molecular link between both observations. Insufficient cellular glucose uptake triggers increased ferritin expression, leading to depletion of the cellular free iron pool and stabilization of the hypoxia-induced factor (HIF) 1α. This transcription factor induces the expression of the glucose transporters (Glut) 1 and 3 and shifts the cellular metabolism towards glycolysis. If this first line of defense is not adequate for sufficient glucose supply, further reduction of the intracellular iron pool affects the enzymes of the mitochondrial electron transport chain and activates the AMP-activated kinase (AMPK). This enzyme triggers the translocation of Glut4 to the plasma membrane as well as the autophagic recycling of cell components in order to mobilize energy resources. Moreover, AMPK activates the autophagic process of ferritinophagy, which provides free iron urgently needed as a cofactor for the synthesis of heme- and iron-sulfur proteins. Excessive activation of this pathway ends in ferroptosis, a special iron-dependent form of cell death, while hampered AMPK activation steadily reduces the iron pools, leading to hypoferremia with iron sequestration in the spleen and liver. Long-lasting iron depletion affects erythropoiesis and results in anemia of chronic disease, a common condition in patients with AD and its comorbidities. Instead of iron supplementation, drugs, diet, or phytochemicals that improve energy supply and cellular glucose uptake should be administered to counteract hypoferremia and anemia of chronic disease.

Host Soluble Factors Cause Changes in Staphylococcus epidermidis Antibiotic Susceptibility and Biofilm Formation Ability.

Staphylococcus epidermidis is a major nosocomial pathogen with a remarkable ability to adhere to the surfaces of indwelling medical devices and form biofilms. Unlike other nosocomial pathogens, the interaction of S. epidermidis with host factors has not been the focus of substantial research. This study aimed to assess the alterations in the antibiotic susceptibility and biofilm formation ability of S. epidermidis in the presence of host serum factors. S. epidermidis strain RP62A was cultured in a laboratory culture medium with or without human serum/plasma, and changes in antibiotic susceptibility, biofilm formation, and gene expression were evaluated. The data obtained revealed that exposure to host serum factors increased the susceptibility of S. epidermidis to glycopeptide antibiotics and was also detrimental to biofilm formation. Gene expression analysis revealed downregulation of both dltA and fmtC genes shortly after human serum/plasma exposure. The importance of transferrin-mediated iron sequestration as a host anti-biofilm strategy against S. epidermidis was also emphasized. We have demonstrated that serum factors play a pivotal role as part of the host's anti-infective strategy against S. epidermidis infections, highlighting the importance of incorporating such factors during in vitro studies with this pathogen.

Keratose Self-Cross-Linked Wound Dressing for Iron Sequestration in Chronic Wounds.

Chronic wound diseases affect a large part of the world population, and therefore, novel treatments are becoming fundamental. People with chronic wounds show high iron and protease levels due to genetic disorders or other comorbidities. Since it was demonstrated that iron plays an important role in chronic wounds, being responsible for oxidative processes (ROS generation), while metalloproteinases prevent wound healing by literally "eating" the growing skin, it is crucial to design an appropriate wound dressing. In this paper, a novel bioactive dressing for binding iron in chronic wounds has been produced. Wool-derived keratose wound dressing in the form of films has been prepared by casting an aqueous solution of keratoses. These films are water-soluble; therefore, in order to increase their stability, they have been made insoluble through a thermal cross-link treatment. Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), and thermogravimetric analyzer (TGA) analyses clarified the structure and the properties of the keratose wound dressing films. The capability of this new biomaterial in iron sequestration has been investigated by testing the adsorption of Fe3+ by inductively coupled plasma-optical emission spectrometry (ICP-OES). The results suggest that the keratose cross-linked films can adsorb a large amount of iron (about 85% of the average amount usually present in chronic wounds) following pseudo-second-order kinetics and an intraparticle diffusion model, thus opening new perspectives in chronic wound care. Furthermore, the QSAR Toolbox was applied for conducting in silico tests and for predicting the chemical behavior of the C-Ker-film. All of the data suggest that the keratose bioactive dressing can significantly contribute to wound healing by mechanisms such as iron depletion, acting as a radical scavenger, diminishing the proteolytic damage, acting as a substrate in place of skin, and, finally, promoting tissue regeneration.

Effects of deferoxamine on intrinsic colistin resistance of Proteus mirabilis.

Proteus mirabilis is a common pathogen, which is responsible for urinary tract infections. Iron is a critical element necessary for both humans and pathogens to maintain their biological functions, and iron limitation via chelator agents may be useful in the treatment of infections. The present study aimed to investigate the synergistic interactions between the iron chelator agent deferoxamine (DFO) and the antibacterial drug colistin. The minimum inhibitory concentration (MIC) values of DFO and colistin for P. mirabilis isolates were determined by broth microdilution. The checkerboard technique was used to examine the potential synergy between DFO and colistin. Furthermore, time-kill assays were used for the confirmation of synergy detected by the checkerboard assay, as well as for determining bacteriostatic and bactericidal interactions throughout a 24-h period. As expected, all P. mirabilis isolates were resistant to colistin. DFO did not inhibit P. mirabilis growth when used alone, even at very high doses (10 µg ml-1). Notably, when in combination with DFO, the MIC values of colistin were markedly reduced, and the checkerboard assay results showed synergy between colistin and DFO for all isolates. In addition, in time-kill assays, colistin + DFO exhibited synergistic activity against all strains at most time intervals and concentrations tested. Colistin + DFO showed bactericidal activity at colistin concentrations of 1xMIC and 2xMIC, although a degree of re-growth was observed in one of the strains at 12-24 h. These findings indicated that DFO has the potential for use as an adjunct to colistin through iron sequestration, thus providing synergistic activity to an antibiotic that would not normally be considered a treatment option against P. mirabilis. In vivo experiments in the future may provide useful information on the efficacy of DFO/colistin since these models effectively reflect physiological parameters.

Asbestos and Iron.

Theories of disease pathogenesis following asbestos exposure have focused on the participation of iron. After exposure, an open network of negatively charged functional groups on the fiber surface complexes host metals with a preference for iron. Competition for iron between the host and the asbestos results in a functional metal deficiency. The homeostasis of iron in the host is modified by the cell response, including increased import to correct the loss of the metal to the fiber surface. The biological effects of asbestos develop in response to and are associated with the disruption of iron homeostasis. Cell iron deficiency in the host following fiber exposure activates kinases and transcription factors, which are associated with the release of mediators coordinating both inflammatory and fibrotic responses. Relative to serpentine chrysotile, the clearance of amphiboles is incomplete, resulting in translocation to the mesothelial surface of the pleura. Since the biological effect of asbestos is dependent on retention of the fiber, the sequestration of iron by the surface, and functional iron deficiency in the cell, the greater clearance (i.e., decreased persistence) of chrysotile results in its diminished impact. An inability to clear asbestos from the lower respiratory tract initiates a host process of iron biomineralization (i.e., asbestos body formation). Host cells attempt to mobilize the metal sequestered by the fiber surface by producing superoxide at the phagosome membrane. The subsequent ferrous cation is oxidized and undergoes hydrolysis, creating poorly crystalline iron oxyhydroxide (i.e., ferrihydrite) included in the coat of the asbestos body.

Correlates of Iron, Cobalamin, Folate, and Vitamin A Status among Stunted Children: A Cross-Sectional Study in Uganda.

Micronutrient deficiencies and stunting are prevalent. We assessed correlates of iron, cobalamin, folate, and vitamin A biomarkers in a cross-sectional study of stunted children aged 12-59 months in eastern Uganda. The biomarkers measured were serum ferritin (S-FE), soluble transferrin receptor (S-TfR), retinol binding protein (S-RBP), plasma cobalamin (P-Cob), methylmalonic acid (P-MMA), and folate (P-Fol). Using linear regression, we assessed socio-demography, stunting severity, malaria rapid test, and inflammation as correlates of micronutrient biomarkers. Of the 750 children, the mean (SD) age was 32.0 (11.7) months, and 45% were girls. Iron stores were depleted (inflammation-corrected S-FE < 12 µg/L) in 43%, and 62% had tissue iron deficiency (S-TfR > 8.3 mg/L). P-Cob was low (<148 pmol/L) and marginal (148-221 pmol/L) in 3% and 20%, and 16% had high P-MMA (>0.75 µmol/L). Inflammation-corrected S-RBP was low (<0.7 µmol/L) in 21% and P-Fol (<14 nmol/L) in 1%. Age 24-59 months was associated with higher S-FE and P-Fol and lower S-TfR. Breastfeeding beyond infancy was associated with lower iron status and cobalamin status, and malaria was associated with lower cobalamin status and tissue iron deficiency (higher S-TfR) despite iron sequestration in stores (higher S-FE). In conclusion, stunted children have iron, cobalamin, and vitamin A deficiencies. Interventions addressing stunting should target co-existing micronutrient deficiencies.

Alterations in the gut microbiome implicate key taxa and metabolic pathways across inflammatory arthritis phenotypes.

Musculoskeletal diseases affect up to 20% of adults worldwide. The gut microbiome has been implicated in inflammatory conditions, but large-scale metagenomic evaluations have not yet traced the routes by which immunity in the gut affects inflammatory arthritis. To characterize the community structure and associated functional processes driving gut microbial involvement in arthritis, the Inflammatory Arthritis Microbiome Consortium investigated 440 stool shotgun metagenomes comprising 221 adults diagnosed with rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis and 219 healthy controls and individuals with joint pain without an underlying inflammatory cause. Diagnosis explained about 2% of gut taxonomic variability, which is comparable in magnitude to inflammatory bowel disease. We identified several candidate microbes with differential carriage patterns in patients with elevated blood markers for inflammation. Our results confirm and extend previous findings of increased carriage of typically oral and inflammatory taxa and decreased abundance and prevalence of typical gut clades, indicating that distal inflammatory conditions, as well as local conditions, correspond to alterations to the gut microbial composition. We identified several differentially encoded pathways in the gut microbiome of patients with inflammatory arthritis, including changes in vitamin B salvage and biosynthesis and enrichment of iron sequestration. Although several of these changes characteristic of inflammation could have causal roles, we hypothesize that they are mainly positive feedback responses to changes in host physiology and immune homeostasis. By connecting taxonomic alternations to functional alterations, this work expands our understanding of the shifts in the gut ecosystem that occur in response to systemic inflammation during arthritis.

Iron colloidal transport mechanisms and sequestration of As, Ni, and Cu along AMD-induced environmental gradients

Colloids are common in mine waters and their chemistry and interactions are critical aspects of metal(loid)s cycling. Previous studies mostly focus on the colloidal transport of metal(loid)s in zones where rivers and soil profiles receive acid mine drainage (AMD). However, there is limited knowledge of the colloid and the associated toxic element behavior as the effluent flows through the coal waste dump, where a geochemical gradient is produced due to AMD reacting with waste rocks which have high acid-neutralization effects. Here, we investigated the geochemistry of Fe and co-occurring elements As, Ni, and Cu along the coal waste dump, in aqueous, colloidal, and precipitate phases, using micro/ultrafiltration combined with STEM, AFM-nanoIR, SEM-EDS, XRD, and FTIR analysis. The results demonstrated that a fast attenuation of H+, SO42−, and metal(loid)s happened as the effluent flowed through the waste-rock dump. The Fe, As, Ni, and Cu were distributed across all colloidal sizes and primarily transported in the nano-colloidal phase (3 kDa–0.1 μm). An increasing pH induced a higher percentage of large Fe colloid fractions (> 0.1 μm) associated with greater sequestration of trace metals, and the values for As from 39.5 % to 54.4 %, Ni from 40.8 % to 75.7 %, and Cu from 43.7 % to 56.0 %, respectively. The Fe-bearing colloids in AMD upstream (pH ≤ 3.0) were primarily composed of Fe–O–S and Fe–O–C with minor Al–Si–O and Ca–O–S, while in less acidic and alkaline sections (pH ≥ 4.1), they were composed of Fe–O with minor Ca–O–S. The iron colloid agglomerates associated with As, Ni, and Cu precipitated coupling the transformation of jarosite, and schwertmannite to ferrihydrite, goethite, and gypsum. These results demonstrate that the formation and transformation of Fe-bearing colloids response to this unique geochemical gradient help to understand the natural metal(loid)s attenuation along the coal waste dump.

MsNRAMP2 Enhances Tolerance to Iron Excess Stress in Nicotiana tabacum and MsMYB Binds to Its Promoter.

Iron(Fe) is a trace metal element necessary for plant growth, but excess iron is harmful to plants. Natural resistance-associated macrophage proteins (NRAMPs) are important for divalent metal transport in plants. In this study, we isolated the MsNRAMP2 (MN_547960) gene from alfalfa, the perennial legume forage. The expression of MsNRAMP2 is specifically induced by iron excess. Overexpression of MsNRAMP2 conferred transgenic tobacco tolerance to iron excess, while it conferred yeast sensitivity to excess iron. Together with the MsNRAMP2 gene, MsMYB (MN_547959) expression is induced by excess iron. Y1H indicated that the MsMYB protein could bind to the "CTGTTG" cis element of the MsNRAMP2 promoter. The results indicated that MsNRAMP2 has a function in iron transport and its expression might be regulated by MsMYB. The excess iron tolerance ability enhancement of MsNRAMP2 may be involved in iron transport, sequestration, or redistribution.