The DOI matches its Crossref record; 152 of the 154 references it cites were found in a registry or an index.
Nutritional immunity: transition metals at the pathogen–host interface
Open accessAbstract
Transition metals occupy an essential niche in biological systems. Their electrostatic properties stabilize substrates or reaction intermediates in the active sites of enzymes, and their heightened reactivity is harnessed for catalysis. However, this heightened activity also renders transition metals toxic at high concentrations. Bacteria, like all living organisms, must regulate their intracellular levels of these elements to satisfy their physiological needs while avoiding harm. It is therefore not surprising that the host capitalizes on both the essentiality and toxicity of transition metals to defend against bacterial invaders. This Review discusses established and emerging paradigms in nutrient metal homeostasis at the pathogen-host interface.
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In the citing paper
“Haptoglobin and haemopexin rapidly bind hemoglobin and haem released from erythrocytes respectively for iron recycling and to possible avoid toxicity posed by free haem (Kumar and Bandyopadhyay, 2005; Hood and Skaar, 2012).”
From Iron at the Centre of Candida albicans Interactions (2018) · cites this paper as Hood and Skaar, 2012
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Fe is a redox- active trace metal that has important roles in most biological systems, supporting vital processes such as DNA replication, transcription and central metabolism 9 .”
From Nutritional immunity: the battle for nutrient metals at the host–pathogen interface (2022) · cites this paper as [9]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Due to host nutritional immunity and iron (Fe) sequestration, S. aureus experiences Fe limitation during infection.”
From The oxidative stress regulator, PerR, is required for staphyloferrin B-mediated iron acquisition in Staphylococcus aureus (2026) · cites this paper as [7]
The cited source says what the claim attributes to it.
In the citing paper
“Although iron is abundant within the earth crust, in the human host, iron is a highly restricted nutrient (Frey and Reed, 2012; Hood and Skaar, 2012).”
From Iron at the Centre of Candida albicans Interactions (2018) · cites this paper as Hood and Skaar, 2012
The cited source says what the claim attributes to it.
In the citing paper
“The concerted action of these proteins renders host Fe pools largely inaccessible to bacteria that lack highaffinity Fe uptake pathways or systems 9,12,14 .”
From Nutritional immunity: the battle for nutrient metals at the host–pathogen interface (2022) · cites this paper as [9]
The cited source says what the claim attributes to it.
In the citing paper
“Vertebrates have developed numerous strategies to starve bacteria of nutrient metals via a process termed nutritional immunity 6,9,10 .”
From Nutritional immunity: the battle for nutrient metals at the host–pathogen interface (2022) · cites this paper as [9]
The cited source says what the claim attributes to it.
In the citing paper
“The prominent strategies that bacteria use to acquire Fe include the secretion of siderophores and the uptake of siderophore-Fe, haem-Fe or kinetically labile ferrous Fe (ref. 9 ) .”
From Nutritional immunity: the battle for nutrient metals at the host–pathogen interface (2022) · cites this paper as [9]
In the citing paper
“This is an innate defense mechanism known as ‘nutritional immunity’.101”
From Iron metabolism and iron disorders revisited in the hepcidin era (2020) · cites this paper as [101]
In the citing paper
“Two of these proteins, S100A8 and S100A9, form a heterodimeric complex named calprotectin and are mainly expressed by PMN.”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [233]
In the citing paper
“Bacterial periplasmic superoxide-dismutases (SOD) contain zinc or manganese to elaborate their defense against host-mediated oxidative stress, and bacteria thus have a certain need for these metals (233).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [233]
In the citing paper
“In addition, copper plays important roles as a prostethic group for many enzymes such as cytochromes, proteins involved in oxidative phosphorylation or copper/zinc-superoxide dismutase (233).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [233]
In the citing paper
“In addition, S100 proteins can be induced by IL-17 and IL-22, and S100 proteins exert pro-inflammatory activity and may promote chemotaxis of PMN (233, 244).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [233]
In the citing paper
“Components of the S100 protein family bind Zn+2, Cu+2, and Mn+2, which thereby exert anti-microbial activity (233).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [233]
In the citing paper
“Nutritional immunity, a strategy of the immune system to deprive essential nutrients, such as divalent metals including iron, from invading pathogens”
From Iron in immune cell function and host defense (2021) · cites this paper as [16]
In the citing paper
“Nutritional immunity, a strategy of the immune system to deprive essential nutrients, such as divalent metals including iron, from invading pathogens [16,17], has played a fundamental role in survival of primate populations challenged by microbes.”
From Iron in immune cell function and host defense (2021) · cites this paper as [16]
In the citing paper
“The sequestration of free iron by host proteins simultaneously prevents acquisition by microbes, a protective effect termed nutritional immunity (see Glossary) 5, 6.”
From Buried Treasure: Evolutionary Perspectives on Microbial Iron Piracy (2015) · cites this paper as [5]
In the citing paper
“The sequestration of essential iron has emerged as a crucial innate defense system termed nutritional immunity”
From Buried Treasure: Evolutionary Perspectives on Microbial Iron Piracy (2015) · cites this paper as [5]
In the citing paper
“An important host defense strategy against infection, known as “nutritional immunity,” relies on the sequestration of essential molecules, such as iron, preventing the growth of pathogens (2).”
From Iron- and Hepcidin-Independent Downregulation of the Iron Exporter Ferroportin in Macrophages during Salmonella Infection (2017) · cites this paper as [2]
In the citing paper
“where competition for limited Fe resources emerged as an evolutionary conserved host defense strategy against infection in plants (2) and animals (3–5) as well as a microbial virulence factor (6).”
From Innate Nutritional Immunity (2018) · cites this paper as [4]
In the citing paper
“Presumably, this explains why most pathogens evolved a variety of strategies aimed at diverting Fe from their hosts into their own metabolic pathways, while hosts co-evolved strategies to restrict pathogens from accessing Fe (3–6).”
From Innate Nutritional Immunity (2018) · cites this paper as [4]
In the citing paper
“Nutritional immunity has since been expanded to include the host processes that manipulate local levels of manganese, zinc, and other transition metals in order to metal starve or intoxicate the invading pathogens”
From Heme Synthesis and Acquisition in Bacterial Pathogens (2016) · cites this paper as [16]
In the citing paper
“The limited access of pathogens to metals serves as an antimicrobial strategy and limits bacterial replication.”
From Heme Synthesis and Acquisition in Bacterial Pathogens (2016) · cites this paper as [16]
In the citing paper
“Thirty years later, Eugene Weinberg popularized the term nutritional immunity to describe the phenomenon, which has since been expanded to include host restriction of zinc, manganese, and nonmetal nutrients such as amino acids (65, 140, 149).”
From Transition Metals and Virulence in Bacteria (2016) · cites this paper as [65]
In the citing paper
“Conflict exists between hosts and invading pathogens over the control of the critical micronutrient, iron (reviewed in [8,9]).”
From Rapidly Escalating Hepcidin and Associated Serum Iron Starvation Are Features of the Acute Response to Typhoid Infection in Humans (2015) · cites this paper as [9]
In the citing paper
“iron and other components of nutritional immunity (e.g., zinc) regulate essential metabolic and inflammatory pathways in immune cells that are largely uncharacterized (365, 599).”
From Aspergillus fumigatus and Aspergillosis in 2019 (2019) · cites this paper as [365]
In the citing paper
“Most TFs are zinc-dependent proteins, and almost 50% of all eukaryotic enzymes are zinc-containing proteins (365).”
From Aspergillus fumigatus and Aspergillosis in 2019 (2019) · cites this paper as [365]
In the citing paper
“apart from inhibiting pathogen growth, iron and other components of nutritional immunity (e.g., zinc) regulate essential metabolic and inflammatory pathways in immune cells that are largely uncharacterized (365, 599).”
From Aspergillus fumigatus and Aspergillosis in 2019 (2019) · cites this paper as [365]
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Metadata
- Authors
- Hood, M. I., & Skaar, E. P.
- Affiliations
- Vanderbilt University (US)
- Corresponding author
- Skaar, Eric P.
- ORCID
- Skaar, Eric P.
- Venue
- Nature Reviews Microbiology
- Published
- 2012-07-16
- Volume
- 10
- Issue
- 8
- Pages
- 525-537
- ISSN
- 1740-1526 (ISSN-L)
- 1740-1534
- PMC
- PMC3875331
- OpenAlex
- W1964339096
- Cited by
- 1,535
- References
- 154
- Citations by year
- 2026: 132 · 2025: 97 · 2024: 118 · 2023: 107 · 2022: 152 · 2021: 150 · 2020: 129 · 2019: 147 · 2018: 97 · 2017: 115 · 2016: 97 · 2015: 87 · 2014: 52 · 2013: 40 · 2012: 11
- FWCI
- 7.40
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (AI 069233, AI073843, AI091771, R01AI069233, R56AI091771, R01AI073843)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Keywords
- nutritional immunity, transition metals, metal homeostasis, host-pathogen arms race, metal sequestration, metal toxicity
- MeSH terms
- Bacteria, Food, Humans, Metals, Transition Elements, Host-Pathogen Interactions
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