The Iron Tug-of-War between Bacterial Siderophores and Innate Immunity

Iron is necessary for the survival of almost all aerobic organisms. In the mammalian host, iron is a required cofactor for the assembly of functional iron-sulfur (Fe-S) cluster proteins, heme-binding proteins and ribonucleotide reductases that regulate various functions, including heme synthesis, oxygen transport and DNA synthesis. However, the bioavailability of iron is low due to its insolubility under aerobic conditions. Moreover, the host coordinates a nutritional immune response to restrict the accessibility of iron against potential pathogens. To counter nutritional immunity, most commensal and pathogenic bacteria synthesize and secrete small iron chelators termed siderophores. Siderophores have potent affinity for iron, which allows them to seize the essential metal from the host iron-binding proteins. To safeguard against iron thievery, the host relies upon the innate immune protein, lipocalin 2 (Lcn2), which could sequester catecholate-type siderophores and thus impede bacterial growth. However, certain bacteria are capable of outmaneuvering the host by either producing “stealth” siderophores or by expressing competitive antagonists that bind Lcn2 in lieu of siderophores. In this review, we summarize the mechanisms underlying the complex iron tug-of-war between host and bacteria with an emphasis on how host innate immunity responds to siderophores.

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Metal cofactors trafficking and assembly in the cell: a molecular view

Pure and Applied Chemistry ◽

10.1515/pac-2018-0720 ◽

2019 ◽

Vol 91 (2) ◽

pp. 231-245 ◽

Cited By ~ 1

Author(s):

Francesca Camponeschi ◽

Lucia Banci

Keyword(s):

Metal Ions ◽

Metal Ion ◽

Binding Proteins ◽

Gene Expression Regulation ◽

Iron Sulfur ◽

Individual Metal ◽

Cellular Import ◽

Iron Binding Proteins ◽

Eukaryotic Organisms ◽

Electron Transfer Processes

Abstract Metal ions are essential cofactors required by the proteome of organisms from any kingdom of life to correctly exert their functions. Dedicated cellular import, transport and homeostasis systems assure that the needed metal ion is correctly delivered and inserted into the target proteins and avoid the presence of free metal ions in the cell, preventing oxidative damaging. Among metal ions, in eukaryotic organisms copper and iron are required by proteins involved in absolutely essential functions, such as respiration, oxidative stress protection, catalysis, gene expression regulation. Copper and iron binding proteins are localized in essentially all cellular compartments. Copper is physiologically present mainly as individual metal ion. Iron can be present both as individual metal ion or as part of cofactors, such as hemes and iron-sulfur (Fe-S) clusters. Both metal ions are characterized by the ability to cycle between different oxidation states, which enable them to catalyze redox reactions and to participate in electron transfer processes. Here we describe in detail the main processes responsible for the trafficking of copper and iron sulfur clusters, with particular interest for the structural aspects of the maturation of copper and iron-sulfur-binding proteins.

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The Role of Iron-Binding Proteins in the Survival of Pathogenic Bacteria

Annual Review of Nutrition ◽

10.1146/annurev.nu.14.070194.002351 ◽

1994 ◽

Vol 14 (1) ◽

pp. 471-493 ◽

Cited By ~ 78

Author(s):

T A Mietzner ◽

S A Morse

Keyword(s):

Pathogenic Bacteria ◽

Binding Proteins ◽

Iron Binding ◽

Iron Binding Proteins

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Ability ofVibrio vulnificus to obtain iron from transferrin and other iron-binding proteins

Current Microbiology ◽

10.1007/bf01577265 ◽

1987 ◽

Vol 15 (3) ◽

pp. 155-157 ◽

Cited By ~ 26

Author(s):

Linda M. Simpson ◽

James D. Oliver

Keyword(s):

Binding Proteins ◽

Iron Binding ◽

Iron Binding Proteins

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Isolation and Characterization of Bacteriophage ZCSE6 against Salmonella spp.: Phage Application in Milk

Biologics ◽

10.3390/biologics1020010 ◽

2021 ◽

Vol 1 (2) ◽

pp. 164-176

Author(s):

Abdallah S. Abdelsattar ◽

Anan Safwat ◽

Rana Nofal ◽

Amera Elsayed ◽

Salsabil Makky ◽

...

Keyword(s):

Pathogenic Bacteria ◽

Raw Milk ◽

Salmonella Spp ◽

Isolation And Characterization ◽

Food Borne ◽

Wide Range ◽

Almost All ◽

And Control ◽

Milk And Dairy Products

Food safety is very important in the food industry as most pathogenic bacteria can cause food-borne diseases and negatively affect public health. In the milk industry, contamination with Salmonella has always been a challenge, but the risks have dramatically increased as almost all bacteria now show resistance to a wide range of commercial antibiotics. This study aimed to isolate a bacteriophage to be used as a bactericidal agent against Salmonella in milk and dairy products. Here, phage ZCSE6 has been isolated from raw milk sample sand molecularly and chemically characterized. At different multiplicities of infection (MOIs) of 0.1, 0.01, and 0.001, the phage–Salmonella interaction was studied for 6 h at 37 °C and 24 h at 8 °C. In addition, ZCSE6 was tested against Salmonella contamination in milk to examine its lytic activity for 3 h at 37 °C. The results showed that ZCSE6 has a small genome size (<48.5 kbp) and belongs to the Siphovirus family. Phage ZCSE6 revealed a high thermal and pH stability at various conditions that mimic milk manufacturing and supply chain conditions. It also demonstrated a significant reduction in Salmonella concentration in media at various MOIs, with higher bacterial eradication at higher MOI. Moreover, it significantly reduced Salmonella growth (MOI 1) in milk, manifesting a 1000-fold decrease in bacteria concentration following 3 h incubation at 37 °C. The results highlighted the strong ability of ZCSE6 to kill Salmonella and control its growth in milk. Thus, ZCSE6 is recommended as a biocontrol agent in milk to limit bacterial growth and increase the milk shelf-life.

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Distribution of iron and iron-binding proteins in first trimester human pregnancies

Placenta ◽

10.1016/s0143-4004(05)80054-2 ◽

1995 ◽

Vol 16 (6) ◽

pp. A.24

Keyword(s):

Binding Proteins ◽

First Trimester ◽

Iron Binding ◽

Iron Binding Proteins

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Deficiency of innate immunity against P. aeruginosa enhances behavioral avoidance via the HECW-1/NPR-1 module in C. elegans

Infection and Immunity ◽

10.1128/iai.00067-21 ◽

2021 ◽

Author(s):

Hua Bai ◽

Wei Zou ◽

Wenhui Zhou ◽

Keqin Zhang ◽

Xiaowei Huang

Keyword(s):

Innate Immunity ◽

Pathogenic Bacteria ◽

Immune Gene ◽

Biological Processes ◽

Defensive Strategy ◽

C Elegans ◽

Defensive Strategies ◽

Behavioral Avoidance ◽

Neuropeptide Y Receptor ◽

G Protein Coupled

To antagonize infection of pathogenic bacteria in soil and confer increased survival, Caenorhabditis elegans employs innate immunity and behavioral avoidance synchronously as the two main defensive strategies. Although both biological processes and their individual signaling pathways have been partially elucidated, knowledge of their interrelationship remains limited. The current study reveals that deficiency of innate immunity triggered by mutation of the classic immune gene pmk-1 promotes avoidance behavior in C. elegans ; and vice versa. Restoration of pmk-1 expression using the tissue-specific promoters suggested that the functional loss of both intestinal and neuronal pmk-1 is necessary for the enhanced avoidance. Additionally, PMK-1 co-localized with the E3 ubiquitin ligase HECW-1 in OLL neurons and regulated the expressional level of the latter, which consequently affected the production of NPR-1, a G-protein-coupled receptor homologous to the mammalian neuropeptide Y receptor, in RMG neurons in a non-cell-autonomous manner. Collectively, our study illustrates, once the innate immunity is impaired when C. elegans antagonizes bacterial infection, the other defensive strategy of behavioral avoidance can be enhanced accordingly via the HECW-1/NPR-1 module, suggesting that GPCRs in neural circuits may receive the inputs from immune system and integrate those two systems for better adapting to the real-time status.

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ANALYSIS OF THE EFFECTIVENESS OF IMMUNOTHERAPY USING AN AUTOLOGOUS COMPLEX OF IMMUNOPEPTIDES IN THE SURGICAL TREATMENT OF PERIODONTITIS

Periódico Tchê Química ◽

10.52571/ptq.v17.n35.2020.34_sevbitov_pgs_381_390.pdf ◽

2020 ◽

Vol 17 (35) ◽

pp. 381-390

Author(s):

Andrei SEVBITOV ◽

Alla DAVIDYANTS ◽

Roman BALYKIN ◽

Anton TIMOSHIN ◽

Mariya KUZNETSOVA

Keyword(s):

Innate Immunity ◽

Surgical Treatment ◽

Bone Tissue ◽

Pathogenic Bacteria ◽

Alveolar Bone ◽

The State ◽

The Body ◽

Immunological Methods ◽

Periodontal Tissues ◽

Antimicrobial Protection

Periodontal disease in the adult population is one of the most pressing problems of dentistry around the world. Thanks to the introduction of modern technologies in practice, it was possible to identify the main mechanisms of the development of this disease at the molecular and genetic level. The interaction of periodontal pathogens with immune factors of antimicrobial protection of the body is the basis of periodontal tissue inflammation and further leads to the destruction of the alveolar bone. Epithelial cells of the gum mucosa play a crucial role against periodontal pathogenic bacteria. Factors of innate immunity play a role not only in antimicrobial protection, but they also support the conditions necessary for the healing and regeneration of periodontal tissues. Therefore, various therapeutic approaches that affect the factors of innate immunity are considered as effective and promising. Clinical examination and determination of factors of innate immunity were performed in 115 patients. Healthy individuals made up a group of 30 people. Patients with chronic generalized periodontitis with varying degrees of severity were 85 people. Each patient underwent orthopantomography on the orthopantomograph Orthophosis XG DS/Ceph (SIRONA Dental System GmbH, Germany) in order to assess the state of the bone tissue of the jaws (the degree of destruction of the cortical layer, the degree of resorption of the interalveolar partitions). Targeted intraoral radiographs were used to assess the state of bone tissue and the quality of surgical treatment. Immunological methods of research were carried out in several stages. The findings of this article make the claim that the use of autologous complex immunopeptides in the surgical treatment of periodontitis reduces the time of achieving a therapeutic effect 2 times, resulting in the rapid relief of the symptoms of inflammation and acceleration of reparative processes.

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