Mechanism Of Iron Transport Research Articles

The Intersection of the Oral Microbiome and Salivary Metabolites in Head and Neck Cancer: From Diagnosis to Treatment

Head and neck cancers (HNCs) are the seventh most common cancer worldwide, accounting for 4–5% of all malignancies. Salivary metabolites, which serve as key metabolic intermediates and cell-signalling molecules, are emerging as potential diagnostic biomarkers for HNC. While current research has largely concentrated on these metabolites as biomarkers, a critical gap remains in understanding their fluctuations before and after treatment, as well as their involvement in oral side effects. Recent studies emphasise the role of the oral microbiome and its metabolic activity in cancer progression and treatment efficacy by bacterial metabolites and virulence factors. Oral bacteria, such as P. gingivalis and F. nucleatum, contribute to a pro-inflammatory environment that promotes tumour growth. Additionally, F. nucleatum enhances its virulence through flagellar assembly and iron transport mechanisms, facilitating tumour invasion and survival. Moreover, alterations in the oral microbiome can influence chemotherapy efficacy and toxicity through the microbiota–host irinotecan axis, highlighting the complex interplay between microbial communities and therapeutic outcomes. Salivary metabolite profiles are influenced by factors such as gender, methods, and patient habits like smoking—a major risk factor for HNC. Radiotherapy (RT), a key treatment for HNC, often causes side effects such as xerostomia, oral mucositis, and swallowing difficulties which impact survivors’ quality of life. Intensity-modulated radiotherapy (IMRT) aims to improve treatment outcomes and minimise side effects but can still lead to significant salivary gland dysfunction and associated complications. This review underscores the microbial and host interactions affecting salivary metabolites and their implications for cancer treatment and patient outcomes.

The effect of iron status on gadolinium deposition in the rat brain: mechanistic implications.

Introduction: Sites associated with gadolinium (Gd) deposition in the brain (e.g., the globus pallidus) are known to contain high concentrations of ferric iron. There is considerable debate over the mechanism of Gd deposition in the brain. The role of iron transport mechanisms in Gd deposition has not been determined. Thus, we seek to identify if Gd deposition can be controlled by modifying iron exposure. Methods: Female Sprague-Dawley rats were given diets with controlled iron levels at 2-6ppm, 6ppt (20g/kg Fe carbonyl) or 48ppm for 3weeks to induce iron deficiency, overload or normalcy. They were kept on those diets while receiving a cumulative 10mmol/kg dose of gadodiamide intravenously over 2weeks, then left to washout gadodiamide for 3days or 3weeks before tissues were harvested. Gd concentrations in tissues were analyzed by ICP-MS. Results: There were no significant effect of dietary iron and total Gd concentrations in the organs, but there was a significant effect of iron status on Gd distribution in the brain. For the 3-week washout cohort, there was a non-significant trend of increasing total brain deposition and decreasing dietary iron, and about 4-fold more Gd in the olfactory bulbs of the low iron group compared to the other groups. Significant brain accumulation was observed in the low iron group total brain Gd in the 3-week washout group relative to the 3-day washout group and no accumulation was observed in other tissues. There was a strong negative correlation between femur Gd concentrations and concentrations in other organs when stratifying by dietary iron. Discussion: Gd brain deposition from linear Gd-based contrast agents (GBCAs) are dependent upon iron status, likely through variable transferrin saturation. This iron dependence appears to be associated with redistribution of peripheral deposited Gd (e.g., in the bone) into the brain.

Mechanism of Iron Transport in the Triticum aestivum L.–Soil System: Perception from a Pot Experiment

Iron is one of the necessary trace elements for plant growth and the human body. The ‘hidden hunger’ phenomenon in the human body caused by an imbalance of iron in soil is increasingly prominent. Addressing this issue and optimizing soil through regulatory measures to improve the absorption and utilization of iron by crops has become an urgent priority in agricultural development. This study carries out pot experiments to observe the growth process of Triticum aestivum L. under various soil iron environments. Combined with previous research results, the transport mechanism of iron in the soil—Triticum aestivum L. system was systematically explored. The results indicate that during the jointing and maturity stages of Triticum aestivum L., iron was preferentially enriched in the underground parts; at the maturity stage, the iron content in various organs of Triticum aestivum L. shows a trend of increase followed by a decrease with the soil iron content varying in the following sequence: deficient, moderately deficient, medium, moderately adequate, and adequate. The iron-deficient stress environment causes an increase in the effectiveness of rhizosphere iron, resulting in a higher level of iron in the plant stems, leaves, and seeds. Conversely, when the soil iron content is medium or adequate, the effectiveness of rhizosphere iron decreases, leading to a reduction in the iron content in each part of the plant. A concentration gradient of 7.2 mg/kg in the experimental setup is found to be the most favorable to the enrichment of iron in the shoots of Triticum aestivum L. plants. The findings of this experiment provide guidance for the fertilization strategy to mitigate iron deficiency symptoms in plants under similar acidic-alkaline conditions of soil, as well as a systematic mechanism reference and basis for studying the soil-plant-human health relationship.

Plasmids in the human gut reveal neutral dispersal and recombination that is overpowered by inflammatory diseases

Plasmids are pivotal in driving bacterial evolution through horizontal gene transfer. Here, we investigated 3467 human gut microbiome samples across continents and disease states, analyzing 11,086 plasmids. Our analyses reveal that plasmid dispersal is predominantly stochastic, indicating neutral processes as the primary driver of their wide distribution. We find that only 20-25% of plasmid DNA is being selected in various disease states, constraining its distribution across hosts. Selective pressures shape specific plasmid segments with distinct ecological functions, influenced by plasmid mobilization lifestyle, antibiotic usage, and inflammatory gut diseases. Notably, these elements are more commonly shared within groups of individuals with similar health conditions, such as Inflammatory Bowel Disease (IBD), regardless of geographic location across continents. These segments contain essential genes such as iron transport mechanisms- a distinctive gut signature of IBD that impacts the severity of inflammation. Our findings shed light on mechanisms driving plasmid dispersal and selection in the human gut, highlighting their role as carriers of vital gene pools impacting bacterial hosts and ecosystem dynamics.

Molecular Mechanisms of Iron Transport and Homeostasis Regulated by Antarctic Krill-Derived Heptapeptide-Iron Complex.

In this study, the molecular mechanisms of iron transport and homeostasis regulated by the Antarctic krill-derived heptapeptide-iron (LVDDHFL-iron) complex were explored. LVDDHFL-iron significantly increased the hemoglobin, serum iron, total iron binding capacity levels, and iron contents in the liver and spleen to normal levels, regulated the gene expressions of iron homeostasis, and enhanced in vivo antioxidant capacity in iron-deficiency anemia mice (P < 0.05). The results revealed that iron ions within LVDDHFL-iron can be transported via the heme transporter and divalent metal transporter-1, and the absorption of LVDDHFL-iron involved receptor-mediated endocytosis. We also found that the transport of LVDDHFL-iron across cells via phagocytosis was facilitated by the up-regulation of the high mobility group protein, heat shock protein β, and V-type proton ATPase subunit, accompanied by the regulatory mechanism of autophagy. These findings provided deeper understandings of the mechanism of LVDDHFL-iron facilitating iron absorption.

Expression and mutagenesis studies in the Medicago truncatula iron transporter MtVTL8 confirm its role in symbiotic nitrogen fixation and reveal amino acids essential for transport.

The model legume Medicago truncatula establishes a symbiosis with soil bacteria (rhizobia) that carry out symbiotic nitrogen fixation (SNF) in plant root nodules. SNF requires the exchange of nutrients between the plant and rhizobia in the nodule that occurs across a plant-derived symbiosome membrane. One iron transporter, belonging to the Vacuolar iron Transporter-Like (VTL) family, MtVTL8, has been identified as essential for bacteria survival and therefore SNF. In this work we investigated the spatial expression of MtVTL8 in nodules and addressed whether it could be functionally interchangeable with a similar nodule-expressed iron transporter, MtVTL4. Using a structural model for MtVTL8 and the previously hypothesized mechanism for iron transport in a phylogenetically-related Vacuolar Iron Transporter (VIT), EgVIT1 with known crystal structure, we identified critical amino acids and obtained their mutants. Mutants were tested in planta for complementation of an SNF defective line and in an iron sensitive mutant yeast strain. An extended phylogenetic assessment of VTLs and VITs showed that amino acids critical for function are conserved differently in VTLs vs. VITs. Our studies showed that some amino acids are essential for iron transport leading us to suggest a model for MtVTL8 function, one that is different for other iron transporters (VITs) studied so far. This study extends the understanding of iron transport mechanisms in VTLs as well as those used in SNF.

TauSTED super-resolution imaging of labile iron in primary hippocampal neurons.

Iron dyshomeostasis is involved in many neurological disorders, particularly neurodegenerative diseases where iron accumulates in various brain regions. Identifying mechanisms of iron transport in the brain is crucial for understanding the role of iron in healthy and pathological states. In neurons, it has been suggested that iron can be transported by the axon to different brain regions in the form of labile iron; a pool of reactive and exchangeable intracellular iron. Here we report a novel approach to imaging labile ferrous iron, Fe(II), in live primary hippocampal neurons using confocal and TauSTED (stimulated emission depletion) microscopy. TauSTED is based on super-resolution STED nanoscopy, which combines high spatial resolution imaging (<40nm) with fluorescence lifetime information, thus reducing background noise and improving image quality. We applied TauSTED imaging utilizing biotracker FerroFarRed Fe(II) and found that labile iron was present as submicrometric puncta in dendrites and axons. Some of these iron-rich structures are mobile and move along neuritic pathways, arguing for a labile iron transport mechanism in neurons. This super-resolution imaging approach offers a new perspective for studying the dynamic mechanisms of axonal and dendritic transport of iron at high spatial resolution in living neurons. In addition, this methodology could be transposed to the imaging of other fluorescent metal sensors.

2118. Comparative Analysis of Cefiderocol Mono- and Combination Therapy for Multi-Drug Resistant Gram-negative Infections

Abstract Background Multi-drug resistant gram-negative infections are a growing concern, necessitating the development of novel treatments. Cefiderocol (CFDC) is a new siderophore cephalosporin that targets the iron transport mechanism used by many gram-negative pathogens. We aimed to compare the clinical outcomes of CFDC monotherapy and combination therapy in various infection types. Methods We performed a retrospective cohort analysis at 5 academic medical centers from May 2022 to April 2023. Patients were included if they were ≥18 years old and received CFDC for ≥48 hours, excluding subsequent courses not separated by ≥90 days. The primary objective was composite clinical success (30-day survival, absence of 30-day infection recurrence and resolution of signs and symptoms), with secondary objectives including individual components of clinical success, on-treatment resistance, 30-day readmission, and adverse reactions. Descriptive statistics and logistic regression were used. Results We analyzed 70 patients, with 35 in each treatment group. The cohort was predominantly male (64.3%), had a mean age of 55.5 years (17.6), and 67% were admitted to the Intensive Care Unit. The mean (SD) APACHE II scores were 12.8 (7.5) for monotherapy and 14.9 (6.7) for combination therapy (p=0.22), while the mean (SD) Charlson comorbidity scores were 5.0 (3.6) and 4.5 (3.5) for the respective groups (p=0.61). The most common infection source was respiratory tract (54.3%), with Pseudomonas aeruginosa (55.7%) and Acinetobacter baumannii (25.7%) as the most frequently isolated pathogens. The median (IQR) CFDC mean inhibitory concentration (MIC) was 0.5 µg/mL (0.25-1.0). The 30-day mortality rates for the monotherapy and combination groups were 20% and 28.6%, respectively. There was no significant difference in composite clinical success between the groups (p=0.59). Conclusion Our preliminary data suggest that there is no difference in clinical success between CFDC monotherapy and combination therapy with another antibiotic. Further studies are needed to confirm these findings and evaluate the optimal use of CFDC in a variety of clinical settings. Disclosures Michael J. Rybak, PharmD, PhD, MPH, Abbvie, Merck, Paratek, Shionogi, Entasis, La Jolla, T2 Biosystems: Advisor/Consultant

Melatonin Promotes Iron Reactivation and Reutilization in Peach Plants under Iron Deficiency.

The yellowing of leaves due to iron deficiency is a prevalent issue in peach production. Although the capacity of exogenous melatonin (MT) to promote iron uptake in peach plants has been demonstrated, its underlying mechanism remains ambiguous. This investigation was carried out to further study the effects of exogenous MT on the iron absorption and transport mechanisms of peach (Prunus persica) plants under iron-deficient conditions through transcriptome sequencing. Under both iron-deficient and iron-supplied conditions, MT increased the content of photosynthetic pigments in peach leaves and decreased the concentrations of pectin, hemicellulose, cell wall iron, pectin iron, and hemicellulose iron in peach plants to a certain extent. These effects stemmed from the inhibitory effect of MT on the polygalacturonase (PG), cellulase (Cx), phenylalanine ammonia-lyase (PAL), and cinnamoyl-coenzyme A reductase (CCR) activities, as well as the promotional effect of MT on the cinnamic acid-4-hydroxylase (C4H) activity, facilitating the reactivation of cell wall component iron. Additionally, MT increased the ferric-chelate reductase (FCR) activity and the contents of total and active iron in various organs of peach plants under iron-deficient and iron-supplied conditions. Transcriptome analysis revealed that the differentially expressed genes (DEGs) linked to iron metabolism in MT-treated peach plants were primarily enriched in the aminoacyl-tRNA biosynthesis pathway under iron-deficient conditions. Furthermore, MT influenced the expression levels of these DEGs, regulating cell wall metabolism, lignin metabolism, and iron translocation within peach plants. Overall, the application of exogenous MT promotes the reactivation and reutilization of iron in peach plants.

Amyloid-β exposed astrocytes induce iron transport from endothelial cells at the blood-brain barrier by altering the ratio of apo- and holo-transferrin.

Excessive brain iron accumulation is observed early in the onset of Alzheimer's disease, notably prior to widespread proteinopathy. These findings suggest that increases in brain iron levels are due to a dysregulation of the iron transport mechanism at the blood-brain barrier. Astrocytes release signals (apo- and holo-transferrin) that communicate brain iron needs to endothelial cells in order to modulate iron transport. Here we use iPSC-derived astrocytes and endothelial cells to investigate how early-disease levels of amyloid-β disrupt iron transport signals secreted by astrocytes to stimulate iron transport from endothelial cells. We demonstrate that conditioned media from astrocytes treated with amyloid-β stimulates iron transport from endothelial cells and induces changes in iron transport pathway proteins. The mechanism underlying this response begins with increased iron uptake and mitochondrial activity by the astrocytes, which in turn increases levels of apo-transferrin in the amyloid-β conditioned astrocyte media leading to increased iron transport from endothelial cells. These novel findings offer a potential explanation for the initiation of excessive iron accumulation in early stages of Alzheimer's disease. What's more, these data provide the first example of how the mechanism of iron transport regulation by apo- and holo-transferrin becomes misappropriated in disease that can lead to iron accumulation. The clinical benefit from understanding early dysregulation in brain iron transport in AD cannot be understated. If therapeutics can target this early process, they could possibly prevent the detrimental cascade that occurs with excessive iron accumulation.

Genetic Incorporation of Dansylalanine in Human Ferroportin to Probe the Alternating Access Mechanism of Iron Transport.

Ferroportin (Fpn), a member of the major facilitator superfamily (MFS) of transporters, is the only known iron exporter found in mammals and plays a crucial role in regulating cellular and systemic iron levels. MFSs take on different conformational states during the transport cycle: inward open, occluded, and outward open. However, the precise molecular mechanism of iron translocation by Fpn remains unclear, with conflicting data proposing different models. In this work, amber codon suppression was employed to introduce dansylalanine (DA), an environment-sensitive fluorescent amino acid, into specific positions of human Fpn (V46, Y54, V161, Y331) predicted to undergo major conformational changes during metal translocation. The results obtained indicate that different mutants exhibit distinct fluorescence spectra depending on the position of the fluorophore within the Fpn structure, suggesting that different local environments can be probed. Cobalt titration experiments revealed fluorescence quenching and blue-shifts of λmax in Y54DA, V161DA, and Y331DA, while V46DA exhibited increased fluorescence and blue-shift of λmax. These observations suggest metal-induced conformational transitions, interpreted in terms of shifts from an outward-open to an occluded conformation. Our study highlights the potential of genetically incorporating DA into Fpn, enabling the investigation of conformational changes using fluorescence spectroscopy. This approach holds great promise for the study of the alternating access mechanism of Fpn and advancing our understanding of the molecular basis of iron transport.

Plasma non-transferrin-bound iron uptake by the small intestine leads to intestinal injury and intestinal flora dysbiosis in an iron overload mouse model and Caco-2 cells.

Iron overload often occurs during blood transfusion and iron supplementation, resulting in the presence of non-transferrin-bound iron (NTBI) in host plasma and damage to multiple organs, but effects on the intestine have rarely been reported. In this study, an iron overload mouse model with plasma NTBI was established by intraperitoneal injection of iron dextran. We found that plasma NTBI damaged intestinal morphology, caused intestinal oxidative stress injury and reactive oxygen species (ROS) accumulation, and induced intestinal epithelial cell apoptosis. In addition, plasma NTBI increased the relative abundance of Ileibacterium and Desulfovibrio in the cecum, while the relative abundance of Faecalibaculum and Romboutsia was reduced. Ileibacterium may be a potential microbial biomarker of plasma NTBI. Based on the function prediction analysis, plasma NTBI led to the weakening of intestinal microbiota function, significantly reducing the function of the extracellular structure. Further investigation into the mechanism of injury showed that iron absorption in the small intestine significantly increased in the iron group. Caco-2 cell monolayers were used as a model of the intestinal epithelium to study the mechanism of iron transport. By adding ferric ammonium citrate (FAC, plasma NTBI in physiological form) to the basolateral side, the apparent permeability coefficient (Papp) values from the basolateral to the apical side were greater than 3×10-6 cm s-1. Intracellular ferritin level and apical iron concentration significantly increased, and SLC39A8 (ZIP8) and SLC39A14 (ZIP14) were highly expressed in the FAC group. Short hairpin RNA (shRNA) was used to knock down ZIP8 and ZIP14 in Caco-2 cells. Transfection with ZIP14-specific shRNA decreased intracellular ferritin level and inhibited iron uptake. These results revealed that plasma NTBI may cause intestinal injury and intestinal flora dysbiosis due to the uptake of plasma NTBI from the basolateral side into the small intestine, which is probably mediated by ZIP14.

Iron in the Symbiosis of Plants and Microorganisms.

Iron is an essential element for most organisms. Both plants and microorganisms have developed different mechanisms for iron uptake, transport and storage. In the symbiosis systems, such as rhizobia-legume symbiosis and arbuscular mycorrhizal (AM) symbiosis, maintaining iron homeostasis to meet the requirements for the interaction between the host plants and the symbiotic microbes is a new challenge. This intriguing topic has drawn the attention of many botanists and microbiologists, and many discoveries have been achieved so far. In this review, we discuss the current progress on iron uptake and transport in the nodules and iron homeostasis in rhizobia-legume symbiosis. The discoveries with regard to iron uptake in AM fungi, iron uptake regulation in AM plants and interactions between iron and other nutrient elements during AM symbiosis are also summarized. At the end of this review, we propose prospects for future studies in this fascinating research area.

MxFRO4 confers iron and salt tolerance through up-regulating antioxidant capacity associated with the ROS scavenging

Iron is involved in various metabolic pathways of plants. Stress from iron deficiency and toxicity in the soil adversely affects plant growth. Therefore, studying the mechanism of iron absorption and transport by plants is of important for resistance to iron stress and to increase crop yield. In this study, Malus xiaojinensis (a Fe-efficient Malus plant) was used as research material. A ferric reduction oxidase (FRO) family gene member was cloned and named MxFRO4. The MxFRO4 encoded a protein of 697 amino acid residues with a predicted molecular weight of 78.54 kDa and a theoretical isoelectric point of 4.90. A subcellular localization assay showed that the MxFRO4 protein was localized on the cell membrane. The expression of MxFRO4 was enriched in immature leaves and roots of M. xiaojinensis, and was strongly affected by low-iron, high-iron, and salt treatments. After introduction of MxFRO4 into Arabidopsis thaliana, the iron and salt stress tolerance of transgenic A. thaliana was greatly improved. Under exposure to low-iron and high-iron stresses, the primary root length, seedling fresh weight, contents of proline, chlorophyll, and iron, and iron(III) chelation activity of the transgenic lines were significantly increased compared with the wild type. The contents of chlorophyll and proline, and the activities of the antioxidant enzymes superoxide dismutase, peroxidase, and catalase were significantly higher in transgenic A. thaliana overexpressing MxFRO4 under salt stress compared with the wild type, whereas the malondialdehyde content was decreased. These results suggest that MxFRO4 contributes to alleviating the effects of low-iron, high-iron, and salinity stresses in transgenic A. thaliana.

Molecular insights into placental iron transfer mechanisms and maternofetal regulation.

Adequate iron transportation from the mother across the placenta is crucial for fetal growth and establishing sufficient iron stores in neonates at birth. The past decade has marked significant discoveries in iron metabolism with the identification of new players and mechanisms. Immunohistochemical studies rendered valuable data on the localization of substantial iron transporters on placental syncytiotrophoblasts. However, the function and regulation of maternal-placentofetal iron transporters and iron handling is still elusive and requires more attention. A thorough literature review was conducted to gather information about placental iron transfer, the role of regulators and maintenance of iron homeostasis. The role of classical and new players in maternal-fetal iron transport and the regulation in the placenta has been addressed in this review. Animal and human studies have been discussed. The role of placental iron regulation in thalassemia and hemochromatosis pregnancies has been reviewed. The current advances that highlight the mechanisms of placental iron regulation and transport in response to maternal and fetal signals have been presented.

Excessive Erythrocytosis Is Not Associated With Altered Iron Homeostasis in Men From the World's Highest City.

Excessive Erythrocytosis Is Not Associated With Altered Iron Homeostasis in Men From the World's Highest City.

Exosomes are involved in iron transport from human blood–brain barrier endothelial cells and are modified by endothelial cell iron status

Iron is essential for normal brain development and function. Hence, understanding the mechanisms of iron efflux at the blood-brain barrier and their regulation are critical for the establishment of brain iron homeostasis. Here, we have investigated the role of exosomes in mediating the transfer of H-ferritin (FTH1)- or transferrin (Tf)-bound iron across the blood-brain barrier endothelial cells (BBBECs). Our study used ECs derived from human-induced pluripotent stem cells that are grown in bicameral chambers. When cells were exposed to 55Fe-Tf or 55Fe-FTH1, the 55Fe activity in the exosome fraction in the basal chamber was significantly higher compared to the supernatant fraction. Furthermore, we determined that the release of endogenous Tf, FTH1, and exosome number is regulated by the iron concentration of the endothelial cells. Moreover, the release of exogenously added Tf or FTH1 to the basal side via exosomes was significantly higher when ECs were iron loaded compared to when they were iron deficient. The release of exosomes containing iron bound to Tf or FTH1 was independent of hepcidin regulation, indicating this mechanism by-passes a major iron regulatory pathway. A potent inhibitor of exosome formation, GW4869, reduced exosomes released from the ECs and also decreased the Tf- and FTH1-bound iron within the exosomes. Collectively, these results indicate that iron transport across the blood-brain barrier is mediated via the exosome pathway and is modified by the iron status of the ECs, providing evidence for a novel alternate mechanism of iron transport into the brain.

Iron transport mechanism of lactoferrin and its application in food processing

Lactoferrin (LF) is a non-heme protein binding Fe3+ tightly and plays a role in regulating the absorption and metabolism of iron under physiological condition. The absorption of non-heme iron occurs in the duodenum. LF is incorporated as a functional factor of food products during food processing. In this review, we describe the structural and functional changes of LF due to thermal processing of food, as well as the metabolic processes of LF iron binding and release in vivo, which characterizes the value of LF as a food matrix from nutrition and biochemistry and provides a basis for the comprehensive utilization of LF in food.

Drought stress alters iron accumulation in Sorghum bicolor seeds

Sorghum ( Sorghum bicolor L.) is a cultivated food crop with iron-rich seeds that thrives in semi-arid areas. Although the mechanism of iron transport has been investigated in detail at the molecular level, the effects of drought stress on its regulation remain unclear. We cultivated sorghum in a chamber without (control) and with drought stress to determine iron accumulation in seeds. The drought stress treatment significantly increased the iron content by approximately 2-fold in seeds and decreased it by 0.6-fold in leaves. The results of RNA-sequencing leaves indicated that drought stress impaired the expression of genes involved in photosynthesis. This agreed with the finding that drought stress significantly reduced plant biomass. The expression of genes encoding vacuole iron transporter and ferritin were increased under drought stress. These expression profiles were confirmed by quantitative polymerase chain reaction, which indicated that expression of genes encoding the vacuole iron transporter and ferritin was significantly increased in leaves and seeds under drought stress. Furthermore, photosynthesis impaired by drought stress might trigger a disturbance in iron homeostasis. Therefore, increased vacuolar transporters and ferritin transcription might be important for safely storing excess iron. Our data suggested that maintaining iron homeostasis via vacuole iron transporters and ferritin enhances iron accumulation in seeds under drought stress. • Sorghum bicolor is drought stress-tolerant and has iron-enriched seeds • Drought stress enhanced iron accumulation in seeds • Drought stress affected genes associated with iron transport/homeostasis • Drought stress increased vacuole iron transporter and ferritin gene expression • Iron homeostasis might involve iron accumulation in drought-stressed seeds

Genomic and transcriptomic characterization revealed key adaptive mechanisms of Marinobacter hydrocarbonoclasticus NI9 for proliferation and degradation of jet fuel

Marinobacter hydrocarbonoclasticus NI9 has the ability to degrade short-chain alkanes (n-C6 to n-C8), which provides a competitive advantage over other microorganisms. Therefore, we sequenced NI9's genome and analyzed its transcriptome using RNAseq when growing in jet fuel. The genome (3.98 Mb) has at least two alkane monooxygenase genes that are differentially expressed with monooxygenase FH712_RS17105 being highly induced compared to monooxygenase FH712_RS06210. FH712_RS17105 is clustered in an operon with a long-chain-fatty-acid--CoA ligase, an aldehyde dehydrogenase family protein, and rubredoxin. The entire gene cluster was induced along with several dioxygenase and cytochrome P450 genes. Genome analyses further revealed aupA and aupB genes encoding proteins involved in the uptake of micelle-solubilized alkanes. M. hydrocarbonoclasticus NI9 cells achieved fuel tolerance through the activation of efflux pumps and blockage of the efflux pumps with an efflux pump inhibitor significantly reduced NI9 growth in fuel. We identified a fuel-inducible RND-efflux pump, which is an orthologue of the P. aeruginosa MexB. M. hydrocarbonoclasticus NI9 also induced ABC iron transport mechanisms suggesting that there is a high demand for iron during fuel degradation. The results collectively suggest that M. hydrocarbonoclasticus NI9 employ similar adaptive mechanisms to those in P. aeruginosa to proliferate in hydrocarbon-containing environments.