Availability of Ferritin-Bound Iron to Enterobacteriaceae

The sequestration of iron in case of infection, termed nutritional immunity, is an established strategy of host defense. However, the interaction between pathogens and the mammalian iron storage protein ferritin is hitherto not completely understood. To better characterize the function of ferritin i...

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Main Authors: Clemens M. Gehrer, Alexander Hoffmann, Richard Hilbe, Philipp Grubwieser, Anna-Maria Mitterstiller, Heribert Talasz, Ferric C. Fang, Esther G. Meyron-Holtz, Sarah H. Atkinson, Günter Weiss, Manfred Nairz
Format: Article
Language:English
Published: MDPI AG 2022-10-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/21/13087
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author Clemens M. Gehrer
Alexander Hoffmann
Richard Hilbe
Philipp Grubwieser
Anna-Maria Mitterstiller
Heribert Talasz
Ferric C. Fang
Esther G. Meyron-Holtz
Sarah H. Atkinson
Günter Weiss
Manfred Nairz
author_facet Clemens M. Gehrer
Alexander Hoffmann
Richard Hilbe
Philipp Grubwieser
Anna-Maria Mitterstiller
Heribert Talasz
Ferric C. Fang
Esther G. Meyron-Holtz
Sarah H. Atkinson
Günter Weiss
Manfred Nairz
author_sort Clemens M. Gehrer
collection DOAJ
description The sequestration of iron in case of infection, termed nutritional immunity, is an established strategy of host defense. However, the interaction between pathogens and the mammalian iron storage protein ferritin is hitherto not completely understood. To better characterize the function of ferritin in Gram-negative infections, we incubated iron-starved cultures of <i>Salmonella</i> Typhimurium and knockout mutant strains defective for major iron uptake pathways or <i><i>Escherichia coli</i></i> with horse spleen ferritin or ionic iron as the sole iron source. Additionally, we added bovine superoxide dismutase and protease inhibitors to the growth medium to assess the effect of superoxide and bacterial proteases, respectively, on <i>Salmonella</i> proliferation and reductive iron release. Compared to free ionic iron, ferritin-bound iron was less available to <i>Salmonella</i>, but was still sufficient to significantly enhance the growth of the bacteria. In the absence of various iron acquisition genes, the availability of ferritin iron further decreased. Supplementation with superoxide dismutase significantly reduced the growth of the Δ<i>entC</i> knockout strain with holoferritin as the sole iron source in comparison with ionic ferrous iron. In contrast, this difference was not observed in the wildtype strain, suggesting that superoxide dismutase undermines bacterial iron uptake from ferritin by siderophore-independent mechanisms. Ferritin seems to diminish iron availability for bacteria in comparison to ionic iron, and its iron sequestering effect could possibly be enhanced by host superoxide dismutase activity.
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spelling doaj.art-96bc4144f22c402f8a11bae848bad1ee2023-11-24T05:02:15ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123211308710.3390/ijms232113087Availability of Ferritin-Bound Iron to EnterobacteriaceaeClemens M. Gehrer0Alexander Hoffmann1Richard Hilbe2Philipp Grubwieser3Anna-Maria Mitterstiller4Heribert Talasz5Ferric C. Fang6Esther G. Meyron-Holtz7Sarah H. Atkinson8Günter Weiss9Manfred Nairz10Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Medical University of Innsbruck, 6020 Innsbruck, AustriaDepartment of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Medical University of Innsbruck, 6020 Innsbruck, AustriaDepartment of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Medical University of Innsbruck, 6020 Innsbruck, AustriaDepartment of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Medical University of Innsbruck, 6020 Innsbruck, AustriaDepartment of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Medical University of Innsbruck, 6020 Innsbruck, AustriaBiocenter, Institute of Medical Biochemistry, Medical Universitiy of Innsbruck, 6020 Innsbruck, AustriaDepartment of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA 98195-7110, USALaboratory of Molecular Nutrition, Faculty of Biotechnology and Food Engineering, Technion-Israel Institute of Technology, Haifa 32000, IsraelKenya Medical Research Institute (KEMRI), Centre for Geographic Medicine Research Coast, KEMRI-Wellcome Trust Research Programme, Kilifi 80108, KenyaDepartment of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Medical University of Innsbruck, 6020 Innsbruck, AustriaDepartment of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Medical University of Innsbruck, 6020 Innsbruck, AustriaThe sequestration of iron in case of infection, termed nutritional immunity, is an established strategy of host defense. However, the interaction between pathogens and the mammalian iron storage protein ferritin is hitherto not completely understood. To better characterize the function of ferritin in Gram-negative infections, we incubated iron-starved cultures of <i>Salmonella</i> Typhimurium and knockout mutant strains defective for major iron uptake pathways or <i><i>Escherichia coli</i></i> with horse spleen ferritin or ionic iron as the sole iron source. Additionally, we added bovine superoxide dismutase and protease inhibitors to the growth medium to assess the effect of superoxide and bacterial proteases, respectively, on <i>Salmonella</i> proliferation and reductive iron release. Compared to free ionic iron, ferritin-bound iron was less available to <i>Salmonella</i>, but was still sufficient to significantly enhance the growth of the bacteria. In the absence of various iron acquisition genes, the availability of ferritin iron further decreased. Supplementation with superoxide dismutase significantly reduced the growth of the Δ<i>entC</i> knockout strain with holoferritin as the sole iron source in comparison with ionic ferrous iron. In contrast, this difference was not observed in the wildtype strain, suggesting that superoxide dismutase undermines bacterial iron uptake from ferritin by siderophore-independent mechanisms. Ferritin seems to diminish iron availability for bacteria in comparison to ionic iron, and its iron sequestering effect could possibly be enhanced by host superoxide dismutase activity.https://www.mdpi.com/1422-0067/23/21/13087ferritin<i>Salmonella</i> <i>enterica</i> subsp. <i>enterica</i> serovar Typhimurium<i>Escherichia</i> <i>coli</i>nutritional immunitysuperoxide dismutasereactive oxygen species
spellingShingle Clemens M. Gehrer
Alexander Hoffmann
Richard Hilbe
Philipp Grubwieser
Anna-Maria Mitterstiller
Heribert Talasz
Ferric C. Fang
Esther G. Meyron-Holtz
Sarah H. Atkinson
Günter Weiss
Manfred Nairz
Availability of Ferritin-Bound Iron to Enterobacteriaceae
International Journal of Molecular Sciences
ferritin
<i>Salmonella</i> <i>enterica</i> subsp. <i>enterica</i> serovar Typhimurium
<i>Escherichia</i> <i>coli</i>
nutritional immunity
superoxide dismutase
reactive oxygen species
title Availability of Ferritin-Bound Iron to Enterobacteriaceae
title_full Availability of Ferritin-Bound Iron to Enterobacteriaceae
title_fullStr Availability of Ferritin-Bound Iron to Enterobacteriaceae
title_full_unstemmed Availability of Ferritin-Bound Iron to Enterobacteriaceae
title_short Availability of Ferritin-Bound Iron to Enterobacteriaceae
title_sort availability of ferritin bound iron to enterobacteriaceae
topic ferritin
<i>Salmonella</i> <i>enterica</i> subsp. <i>enterica</i> serovar Typhimurium
<i>Escherichia</i> <i>coli</i>
nutritional immunity
superoxide dismutase
reactive oxygen species
url https://www.mdpi.com/1422-0067/23/21/13087
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