Iron at the interface of immunity and infection DOI Creative Commons
Manfred Nairz, David Haschka, Egon Demetz

et al.

Frontiers in Pharmacology, Journal Year: 2014, Volume and Issue: 5

Published: July 16, 2014

Both, mammalian cells and microbes have an essential need for iron, which is required many metabolic processes microbial pathogenicity. In addition, cross-regulatory interactions between iron homeostasis immune function are evident. Cytokines the acute phase protein hepcidin affect leading to retention of metal within macrophages hypoferremia. This considered result from a defense mechanism body limit availability extracellular pathogens while on other hand reduction circulating results in development anemia inflammation. Opposite, erythropoiesis inducing hormone erythropoietin innate responses by influencing interferon-gamma (IFN-γ) mediated (iron) or NF-kB inducible (erythropoietin) effector pathways macrophages. Thus, loaded with lose their ability kill intracellular via IFN-γ such as nitric oxide (NO) formation. Accordingly, invaded bacterium Salmonella enterica serovar Typhimurium increase expression export ferroportin thereby reducing intramacrophage bacteria side strengthening anti-microbial macrophage increased formation NO TNF-α. certain resistance genes natural associated (Nramp1) lipocalin-2 exert part antimicrobial activity controlling host and/or homeostasis. Consequently, pharmacological dietary modification cellular trafficking enhances but may susceptibility compartment vice versa. control over central battlefield host-pathogen interplay course infectious disease favor either pathogenic invader.

Language: Английский

Amplifying STING activation by cyclic dinucleotide–manganese particles for local and systemic cancer metalloimmunotherapy DOI
Xiaoqi Sun, Yu Zhang, Jiaqian Li

et al.

Nature Nanotechnology, Journal Year: 2021, Volume and Issue: 16(11), P. 1260 - 1270

Published: Sept. 30, 2021

Language: Английский

Citations

511
Transcriptional regulation by Ferric Uptake Regulator (Fur) in pathogenic bacteria DOI Creative Commons
Bryan Troxell, Hosni M. Hassan

Frontiers in Cellular and Infection Microbiology, Journal Year: 2013, Volume and Issue: 3

Published: Jan. 1, 2013

In the ancient anaerobic environment, ferrous iron (Fe(2+)) was one of first metal cofactors. Oxygenation world challenged bacteria to acquire insoluble ferric (Fe(3+)) and later defend against reactive oxygen species (ROS) generated by Fenton chemistry. To Fe(3+), produce low-molecular weight compounds, known as siderophores, which have extremely high affinity for Fe(3+). However, during infection host restricts from pathogens producing iron- siderophore-chelating proteins, exporting intracellular pathogen-containing compartments, limiting absorption dietary iron. Ferric Uptake Regulator (Fur) is a transcription factor utilizes Fe(2+) corepressor represses siderophore synthesis in pathogens. Fur, directly or indirectly, controls expression enzymes that protect ROS damage. Thus, challenges homeostasis defense are addressed via Fur. Although role Fur repressor well-documented, emerging evidence demonstrates can function an activator. activation occur through three distinct mechanisms (1) indirectly small RNAs, (2) binding at cis regulatory elements enhance recruitment RNA polymerase holoenzyme (RNAP), (3) functioning antirepressor removing blocking DNA transcription. addition, homologs control peroxide stress (PerR) uptake other metals such zinc (Zur) manganese (Mur) pathogenic bacteria. family members important virulence within bacterial since mutants fur, perR, zur exhibit reduced numerous animal plant models infection. This review focuses on breadth regulation

Language: Английский

Citations

434
A novel mechanism for the biogenesis of outer membrane vesicles in Gram-negative bacteria DOI Creative Commons

Sandro Roier,

Franz G. Zingl, Fatih Çakar

et al.

Nature Communications, Journal Year: 2016, Volume and Issue: 7(1)

Published: Jan. 25, 2016

Bacterial outer membrane vesicles (OMVs) have important biological roles in pathogenesis and intercellular interactions, but a general mechanism of OMV formation is lacking. Here we show that the VacJ/Yrb ABC (ATP-binding cassette) transport system, proposed phospholipid transporter, involved formation. Deletion or repression increases production two distantly related Gram-negative bacteria, Haemophilus influenzae Vibrio cholerae. Lipidome analyses demonstrate OMVs from VacJ/Yrb-defective mutants H. are enriched phospholipids certain fatty acids. Furthermore, regulation system respond to iron starvation. Our results suggest new biogenesis based on accumulation leaflet membrane. This highly conserved among provides means for regulation, can account under all growth conditions, might pathophysiological vivo.

Language: Английский

Citations

411
Beyond iron: non-classical biological functions of bacterial siderophores DOI Creative Commons
Timothy C. Johnstone, Elizabeth M. Nolan

Dalton Transactions, Journal Year: 2015, Volume and Issue: 44(14), P. 6320 - 6339

Published: Jan. 1, 2015

Non-classical siderophores functions are reviewed and evaluated with suggestions for future directions of investigation.

Language: Английский

Citations

376
Protecting the Newborn and Young Infant from Infectious Diseases: Lessons from Immune Ontogeny DOI Creative Commons
Tobias R. Kollmann, Beate Kampmann, Sarkis K. Mazmanian

et al.

Immunity, Journal Year: 2017, Volume and Issue: 46(3), P. 350 - 363

Published: March 1, 2017

Language: Английский

Citations

375
Transition Metals and Virulence in Bacteria DOI Open Access
Lauren D. Palmer, Eric P. Skaar

Annual Review of Genetics, Journal Year: 2016, Volume and Issue: 50(1), P. 67 - 91

Published: Sept. 12, 2016

Transition metals are required trace elements for all forms of life. Due to their unique inorganic and redox properties, transition serve as cofactors enzymes other proteins. In bacterial pathogenesis, the vertebrate host represents a rich source nutrient metals, bacteria have evolved diverse metal acquisition strategies. Host homeostasis changes dramatically in response infections, including production sequestering proteins bombardment with toxic levels metals. response, systems subvert sequestration toxicity. The coevolution hosts pathogens battle has uncovered emerging paradigms social microbiology, rapid evolution, specificity, across domains. This review focuses on recent advances open questions our understanding complex role at host-pathogen interface.

Language: Английский

Citations

371
Faecalibacterium prausnitzii subspecies–level dysbiosis in the human gut microbiome underlying atopic dermatitis DOI Creative Commons

Han Song,

Young Yoo,

Junghyun Hwang

et al.

Journal of Allergy and Clinical Immunology, Journal Year: 2015, Volume and Issue: 137(3), P. 852 - 860

Published: Oct. 2, 2015

Atopic dermatitis (AD) is a serious global epidemic associated with modern lifestyle.Although aberrant interactions between gut microbes and the intestinal immune system have been implicated in this skin disease, nature of microbiome dysfunction underlying disease remains unclear.The from 132 subjects, including 90 patients AD, was analyzed by using 16S rRNA gene metagenome sequence analyses. Reference genomes Human Microbiome Project KEGG Orthology database were used for Short-chain fatty acids fecal samples compared gas chromatographic-mass spectrometric analyses.We show that enrichment subspecies major species Faecalibacterium prausnitzii strongly AD. In addition, AD enriched genes encoding use various nutrients could be released damaged epithelium, reflecting bloom auxotrophic bacteria. Fecal showed decreased levels butyrate propionate, which anti-inflammatory effects. This likely consequence an intraspecies compositional change F reduces number high propionate producers, those related to strain A2-165, lack has Crohn disease.The data suggest feedback dysbiosis dysregulation epithelial inflammation might underlie chronic progression resulting impairment barrier, ultimately leads TH2-type responses allergens skin.

Language: Английский

Citations

365
Mechanistic study on antibacterial action of zinc oxide nanoparticles synthesized using green route DOI
Happy Agarwal,

Soumya Menon,

S. Venkat Kumar

et al.

Chemico-Biological Interactions, Journal Year: 2018, Volume and Issue: 286, P. 60 - 70

Published: March 15, 2018

Language: Английский

Citations

364
Metals to combat antimicrobial resistance DOI Creative Commons
Angelo Frei, Anthony D. Verderosa, Alysha G. Elliott

et al.

Nature Reviews Chemistry, Journal Year: 2023, Volume and Issue: 7(3), P. 202 - 224

Published: Feb. 8, 2023

Bacteria, similar to most organisms, have a love–hate relationship with metals: specific metal may be essential for survival yet toxic in certain forms and concentrations. Metal ions long history of antimicrobial activity received increasing attention recent years owing the rise resistance. The search antibacterial agents now encompasses ions, nanoparticles complexes (‘metalloantibiotics’). Although advanced clinic, metalloantibiotics are vast underexplored group compounds that could lead much-needed new class antibiotics. This Review summarizes developments this growing field, focusing on advances development metalloantibiotics, particular, those which mechanism action has been investigated. We also provide an overview alternative uses combat bacterial infections, including photodynamic therapy radionuclide diagnosis infections. Metals their promising source Their 3D geometry potential multiple mechanisms important assets; however, substantial investment research is needed advance them clinic.

Language: Английский

Citations

363
Molecular basis for manganese sequestration by calprotectin and roles in the innate immune response to invading bacterial pathogens DOI Open Access
Steven M. Damo, Thomas E. Kehl‐Fie, Norie Sugitani

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2013, Volume and Issue: 110(10), P. 3841 - 3846

Published: Feb. 19, 2013

The S100A8/S100A9 heterodimer calprotectin (CP) functions in the host response to pathogens through a mechanism termed "nutritional immunity." CP binds Mn(2+) and Zn(2+) with high affinity starves bacteria of these essential nutrients. Combining biophysical, structural, microbiological analysis, we identified molecular basis sequestration. asymmetry creates single Mn(2+)-binding site from six histidine residues, which distinguishes all other proteins. Analysis mutants altered metal-binding properties revealed that, despite both being metals, maximal growth inhibition multiple bacterial requires These data establish importance sequestration defense against infection, explain broad-spectrum antimicrobial activity relative S100 proteins, clarify impact metal depletion on innate immune infection.

Language: Английский

Citations

356