Iron Transport Machinery: A Potential Therapeutic Target In Escherichia Coli

Iron metabolism is an integral part of life for most organisms. Despite its essentiality, iron can also become toxic. There are many aspects to maintaining iron balance within the cell. The aim of this work is to provide insight into the function of several components involved in bacterial iron homeostasis. This work is significant for the development of novel antibiotics for treating resistant or pathogenic bacteria. Herein, it is shown that nickel can disrupt normal bacterial iron metabolism and that bacterial resistance can be affected by expression of iron acquisition genes. Once iron is obtained by the cell, it can be used to synthesize iron-sulfur clusters which are incorporated into many metalloenzymes. The shuttling of iron-sulfur clusters is carried out by A-Type carrier proteins and glutaredoxins. This important step is required for bacterial cell survival and provides another novel target for the development of drug treatment options

Nickel Exposure Reduces Enterobactin Production in Escherichia Coli

Escherichia coli is a well- studied bacterium that can be found in many niches, such as industrial wastewater, where the concentration of nickel can rise to low- millimolar levels. Recent studies show that nickel exposure can repress pyochelin or induce pyo-verdine siderophore production in Pseudomonas aueroginosa. Understanding the mo-lecular cross- talk between siderophore production, metal homeostasis, and metal toxicity in microorganisms is critical for designing bioremediation strategies for metal- contaminated sites. Here, we show that high- nickel exposure prolongs lag phase duration as a result of low- intracellular iron levels in E. coli. Although E. coli cells respond to low- intracellular iron during nickel stress by maintaining high expres-sion of iron uptake systems such as fepA, the demand for iron is not met due to a lack of siderophores in the extracellular medium during nickel stress. Taken together, these results indicate that nickel inhibits iron accumulation in E. coli by reducing the presence of enterobactin in the extracellular medium

Nickel Exposure Reduces Enterobactin Production in \u3cem\u3eEscherichia coli\u3c/em\u3e

Escherichia coli is a well- studied bacterium that can be found in many niches, such as industrial wastewater, where the concentration of nickel can rise to low- millimolar levels. Recent studies show that nickel exposure can repress pyochelin or induce pyo-verdine siderophore production in Pseudomonas aueroginosa. Understanding the mo-lecular cross- talk between siderophore production, metal homeostasis, and metal toxicity in microorganisms is critical for designing bioremediation strategies for metal- contaminated sites. Here, we show that high- nickel exposure prolongs lag phase duration as a result of low- intracellular iron levels in E. coli. Although E. coli cells respond to low- intracellular iron during nickel stress by maintaining high expres-sion of iron uptake systems such as fepA, the demand for iron is not met due to a lack of siderophores in the extracellular medium during nickel stress. Taken together, these results indicate that nickel inhibits iron accumulation in E. coli by reducing the presence of enterobactin in the extracellular medium. Escherichia coli is a well- studied bacterium that can be found in many niches, such as industrial wastewater, where the concentration of nickel can rise to low-millimolar levels. Recent studies show that nickel exposure can repress pyochelin or induce pyo- verdine siderophore production inPseudomonas aueroginosa. Understanding the mo- lecular cross-talk between siderophore production, metal homeostasis, and metal toxicity in microorganisms is critical for designing bioremediation strategies for metal-contaminated sites. Here, we show that high-nickel exposure prolongs lag phase duration as a result of low- intracellular iron levels in E. coli. Although E. coli cells respond to low- intracellular iron during nickel stress by maintaining high expres- sion of iron uptake systems such as fepA, the demand for iron is not met due to a lack of siderophores in the extracellular medium during nickel stress. Taken together, these results indicate that nickel inhibits iron accumulation inE. coli by reducing the presence of enterobactin inthe extracellular mediu

Nickel exposure reduces enterobactin production in Escherichia coli

Abstract Escherichia coli is a well‐studied bacterium that can be found in many niches, such as industrial wastewater, where the concentration of nickel can rise to low‐millimolar levels. Recent studies show that nickel exposure can repress pyochelin or induce pyoverdine siderophore production in Pseudomonas aueroginosa. Understanding the molecular cross‐talk between siderophore production, metal homeostasis, and metal toxicity in microorganisms is critical for designing bioremediation strategies for metal‐contaminated sites. Here, we show that high‐nickel exposure prolongs lag phase duration as a result of low‐intracellular iron levels in E. coli. Although E. coli cells respond to low‐intracellular iron during nickel stress by maintaining high expression of iron uptake systems such as fepA, the demand for iron is not met due to a lack of siderophores in the extracellular medium during nickel stress. Taken together, these results indicate that nickel inhibits iron accumulation in E. coli by reducing the presence of enterobactin in the extracellular medium

<i>In Vivo</i> Virus-Based Macrofluorogenic Probes Target Azide-Labeled Surface Glycans in MCF‑7 Breast Cancer Cells

Chemical addressability of viral particles has played a pivotal role in adapting these biogenic macromolecules for various applications ranging from medicine to inorganic catalysis. Cowpea mosaic virus possesses multiple features that are advantageous for the next generation of virus-based nanotechnology: consistent multimeric assemblies dictated by its genetic code, facile large scale production, and lack of observable toxicity in humans. Herein, the chemistry of the viral particles is extended with the use of Cu-free strain-promoted azide–alkyne cycloaddition reaction, or SPAAC reaction. The elimination of Cu, its cocatalyst and reducing agent, simplifies the reaction scheme to a more straightforward approach, which can be directly applied to living systems. As a proof of concept, the viral particles modified with the azadibenzylcyclooctyne functional groups are utilized to trigger and amplify a weak fluorescent signal (azidocoumarin) in live cell cultures to visualize the non-natural sugars. Future adaptations of this platform may be developed to enhance biosensing applications

Atp7b-dependent choroid plexus dysfunction causes transient copper deficit and metabolic changes in the developing mouse brain.

Copper (Cu) has a multifaceted role in brain development, function, and metabolism. Two homologous Cu transporters, Atp7a (Menkes disease protein) and Atp7b (Wilson disease protein), maintain Cu homeostasis in the tissue. Atp7a mediates Cu entry into the brain and activates Cu-dependent enzymes, whereas the role of Atp7b is less clear. We show that during postnatal development Atp7b is necessary for normal morphology and function of choroid plexus (ChPl). Inactivation of Atp7b causes reorganization of ChPl' cytoskeleton and cell-cell contacts, loss of Slc31a1 from the apical membrane, and a decrease in the length and number of microvilli and cilia. In ChPl lacking Atp7b, Atp7a is upregulated but remains intracellular, which limits Cu transport into the brain and results in significant Cu deficit, which is reversed only in older animals. Cu deficiency is associated with down-regulation of Atp7a in locus coeruleus and catecholamine imbalance, despite normal expression of dopamine-β-hydroxylase. In addition, there are notable changes in the brain lipidome, which can be attributed to inhibition of diacylglyceride-to-phosphatidylethanolamine conversion. These results identify the new role for Atp7b in developing brain and identify metabolic changes that could be exacerbated by Cu chelation therapy

\u3cem\u3eIn Vivo\u3c/em\u3e Virus-Based Macrofluorogenic Probes Target Azide-Labeled Surface Glycans in MCF-7 Breast Cancer Cells

Chemical addressability of viral particles has played a pivotal role in adapting these biogenic macromolecules for various applications ranging from medicine to inorganic catalysis. The consistent multimeric assemblies dictated by its genetic code, facile large scale production, lack of observable toxicity in humans, Cowpea mosaic virus possesses multiple features that are advantageous for the next generation of virus-based nanotechnology. Herein, the chemistry of the viral particles is extended with the use of Cu-free strain-promoted azide-alkyne cycloaddition reaction, or SPAAC reaction. The elimination of Cu, its co-catalyst and reducing agent simplifies the reaction scheme to a more straightforward approach, which can be directly applied to living systems. As a proof of concept, the viral particles modified with the aza-dibenzylcyclooctynes functional groups are utilized to trigger and amplify a weak fluorescent signal (azidocoumarin) in live cell cultures to visualize the non-natural sugars. Future adaptations of this platform may be developed to enhance biosensing applications