The Battle for Iron between Bacterial Pathogens and Their Vertebrate Hosts
Open accessAbstract
Iron is a vital nutrient for virtually all forms of life.The requirement for iron is based on its role in cellular processes ranging from energy generation and DNA replication to oxygen transport and protection against oxidative stress.Bacterial pathogens are not exempt from this iron requirement, as these organisms must acquire iron within their vertebrate hosts in order to replicate and cause disease.
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Taken together, these factors ensure that vertebrate tissue is virtually devoid of free iron.
“Taken together, these factors ensure that vertebrate tissue is virtually devoid of free iron [21].”
From Strategies of intracellular pathogens for obtaining iron from the environment (2015) · cites this paper as [21]
Hb or heme released as a result of natural erythrocyte lysis is captured by haptoglobin and hemopexin, respectively.
“Hb or heme that is released as a result of natural erythrocyte lysis is captured by haptoglobin and hemopexin, respectively.”
From Strategies of intracellular pathogens for obtaining iron from the environment (2015) · cites this paper as [21]
Any extracellular free Fe is rapidly bound by circulating Tf.
“Any extracellular free Fe is rapidly bound by circulating Tf.”
From Strategies of intracellular pathogens for obtaining iron from the environment (2015) · cites this paper as [21]
In a healthy individual, Fe is largely intracellular, sequestered within Ft or as a cofactor of heme complexed to Hb within erythrocytes.
“In a healthy individual Fe is largely intracellular, sequestered within Ft or as a cofactor of heme complexed to Hb within erythrocytes.”
From Strategies of intracellular pathogens for obtaining iron from the environment (2015) · cites this paper as [21]
This host defense is circumvented through the production of stealth siderophores that are modified to prevent siderocalin binding.
“This host defense is circumvented through the production of stealth siderophores that are modified in such a way as to prevent siderocalin binding [21, 27].”
From Strategies of intracellular pathogens for obtaining iron from the environment (2015) · cites this paper as [21]
Secreted hemophores can remove heme from Hb or hemopexin and deliver heme to bacterial cells through binding with hemophore receptors.
“Analogously, secreted hemophores can remove heme from Hb or hemopexin and deliver heme to bacterial cells through binding with hemophore receptors.”
From Strategies of intracellular pathogens for obtaining iron from the environment (2015) · cites this paper as [21]
During infection, pathogens are capable of altering the battlefield to increase the abundance of potential Fe sources.
“During infection, pathogens are capable of altering the battlefield to increase the abundance of potential Fe sources.”
From Strategies of intracellular pathogens for obtaining iron from the environment (2015) · cites this paper as [21]
Bacterial cytotoxins damage host cells, leading to the release of Ft, while hemolytic toxins from bacteria can lyse erythrocytes, liberating Hb.
“For example, bacterial cytotoxins damage host cells, leading to the release of Ft, while hemolytic toxins from bacteria can lyse erythrocytes, liberating Hb.”
From Strategies of intracellular pathogens for obtaining iron from the environment (2015) · cites this paper as [21]
Siderophores are small ferric iron chelators that bind with extremely high affinity (iron formation constants Kd range from 10−20 to 10−50 M), some of which can extract iron from Tf and Lf.
“Siderophores are small ferric iron chelators that bind with extremely high affinity (iron formation constants K d range from 10−20 to 10−50 M), some of which can extract iron from Tf and Lf [21].”
From Strategies of intracellular pathogens for obtaining iron from the environment (2015) · cites this paper as [21]
Siderophore-mediated Fe acquisition is inhibited by the innate immune protein siderocalin, which binds siderophores and prevents receptor recognition.
“Siderophore mediated Fe acquisition is inhibited by the innate immune protein siderocalin, which binds siderophores and prevents receptor recognition.”
From Strategies of intracellular pathogens for obtaining iron from the environment (2015) · cites this paper as [21]
The resulting inflammatory response includes the release of Lf from secondary granules contained with polymorphonuclear leukocytes (PMNs).
“The resulting inflammatory response includes the release of Lf from secondary granules contained with polymorphonuclear leukocytes (PMNs) [10, 21, 27].”
From Strategies of intracellular pathogens for obtaining iron from the environment (2015) · cites this paper as [21]
Secreted siderophores can remove Fe from Tf, Lf, or Ft, whereupon siderophore-iron complexes are recognized by cognate receptors at the bacterial surface.
“Alternatively, secreted siderophores can remove Fe from Tf, Lf, or Ft, whereupon siderophore-iron complexes are recognized by cognate receptors at the bacterial surface.”
From Strategies of intracellular pathogens for obtaining iron from the environment (2015) · cites this paper as [21]
Later microbiology and molecular genetics showed nutritional immunity is pivotal against bacteria, fungi, and parasites.
“Subsequent microbiology and molecular genetic studies established that nutritional immunity plays a pivotal role in defense against an array of pathogens, including bacteria, fungi, and parasites 3, 15.”
From Buried Treasure: Evolutionary Perspectives on Microbial Iron Piracy (2015) · cites this paper as [15]
In biological systems, available free iron is scarce, and the contest between pathogen and host for iron influences the course of many infections.
“In biological systems, free iron ions are present at extremely low concentrations, and the competition for iron between pathogens and the host is important to the outcome of many infections (4).”
From Hepcidin-mediated iron sequestration protects against bacterial dissemination during pneumonia (2017) · cites this paper as [4]
The battle for iron is a critical component of antimicrobial defenses in many infections.
“Multiple lines of evidence suggest that this battle for iron is a critical component of antimicrobial defenses in many infections [3].”
From Hepcidin and Host Defense against Infectious Diseases (2015) · cites this paper as [3]
Reduction of serum transferrin appears to be one of the mechanisms of microbial iron withdrawal.
“Therefore, the reduction of serum TF appears to be one of the mechanisms of microbial iron withdrawal [54–57].”
From Iron deficiency or anemia of inflammation?: Differential diagnosis and mechanisms of anemia of inflammation (2016) · cites this paper as [57]
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References 27 · Cited by 796
- Authors
- Skaar, E. P.
- Affiliations
- Vanderbilt University Medical Center (US)
- Corresponding author
- Skaar, Eric P.
- ORCID
- Skaar, Eric P.
- Venue
- PLoS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-08-12
- Volume
- 6
- Issue
- 8
- Pages
- e1000949
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC2920840
- OpenAlex
- W2060976020
- Cited by
- 796
- References
- 27
- Citations by year
- 2026: 35 · 2025: 26 · 2024: 39 · 2023: 31 · 2022: 56 · 2021: 76 · 2020: 70 · 2019: 69 · 2018: 83 · 2017: 73 · 2016: 58 · 2015: 53 · 2014: 46 · 2013: 39 · 2012: 22
- FWCI
- 16.26
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Pathogens (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (AI073843, AI057157)
- National Institute of Allergy and Infectious Diseases (AI073843, AI 057157, AI0169233, U54AI057157, R01AI073843)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Escherichia coli research studies
- Keywords
- iron acquisition, pathogenic bacteria, host-pathogen interaction, vertebrate hosts, iron metabolism, bacterial virulence, host defense against infection
- MeSH terms
- Animals, Bacteria, Humans, Iron, Vertebrates, Host-Pathogen Interactions
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