CoChat
Sign Up
Cited by 45Iron Metabolism and DisordersGut microbiota and healthBacterial Genetics and Biotechnology

Iron at the host-microbe interface

Open access
Gerner, Romana R., Nuccio, Sean-Paul, Raffatellu, Manuela·2020·Molecular Aspects of Medicine
DOI 10.1016/j.mam.2020.100895PMC PMC7554189
Open this paper in CoChat — free account

Abstract

Iron is an essential micronutrient for nearly all living organisms. In addition to facilitating redox reactions, iron is bound by metalloproteins that participate in a variety of biological processes. As the bioavailability of free iron in host environments is extremely low, iron lies at the center of a battle for nutrients between microbes and their host. Mucosal surfaces such as the respiratory and gastrointestinal tracts are constantly exposed to commensal and pathogenic microorganisms. Whereas a key strategy of mammalian antimicrobial defense is to deprive microbes of iron, pathogens and some commensals have evolved effective strategies to circumvent iron limitation. Here we provide an overview of mechanisms underpinning the tug-of-war for iron between microbes and their host, with a particular focus on mucosal surfaces.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.mam.2020.100895

Cites

26 of 26 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In human physiology, sequestration of iron is a central feature of nutritional immunity, and pathogens have evolved mechanisms to liberate iron from host stores.

    “In human physiology, sequestration of iron is a central feature of nutritional immunity,120 and pathogens have evolved a wide variety of mechanisms to liberate iron from host stores.121”

    From Metals in Motion: Understanding Labile Metal Pools in Bacteria (2025) · cites this paper as [121]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 61

  1. Bachman MA, Oyler JE, Burns SH, Caza M, Lépine F, Dozois CM, and Weiser JN (2011). Klebsiella pneumoniae Yersiniabactin Promotes Respiratory Tract Infection through Evasion of Lipocalin 2. Infect. Immun. 79, 3309– 3316. 21576334 PMC3147564
  2. Bachman MA, Lenio S, Schmidt L, Oyler JE, and Weiser JN (2012). Interaction of Lipocalin 2, Transferrin, and Siderophores Determines the Replicative Niche of Klebsiella pneumoniae during Pneumonia. MBio 3. PMC3509427 23169997
  3. Bairwa G, Jung WH, and Kronstad JW (2017). Iron acquisition in fungal pathogens of humans. Met. Integr. Biometal Sci. 9, 215– 227. PMC5734051 28217776
  4. Baumler AJ, and Sperandio V (2016). Interactions between the microbiota and pathogenic bacteria in the gut. Nature 535, 85– 93. 27383983 PMC5114849
  5. Belkaid Y, and Hand T (2014). Role of the Microbiota in Immunity and inflammation. Cell 157, 121– 141. 24679531 PMC4056765
  6. Braun V, Pramanik A, Gwinner T, Koberle M, and Bohn E (2009). Sideromycins: tools and antibiotics. Biometals 22, 3– 13. 19130258 PMC2757582
  7. Caruso R, Lo BC, and Núñez G (2020). Host–microbiota interactions in inflammatory bowel disease. Nat. Rev. Immunol. 1– 16. 32005980
  8. Celis AI, and Relman DA (2020). Competitors versus Collaborators: Micronutrient Processing by Pathogenic and Commensal Human-Associated Gut Bacteria. Mol. Cell 78, 570– 576. 32442503
  9. Corbin BD, Seeley EH, Raab A, Feldmann J, Miller MR, Torres VJ, Anderson KL, Dattilo BM, Dunman PM, Gerads R, (2008). Metal Chelation and Inhibition of Bacterial Growth in Tissue Abscesses. Science 319, 962– 965. 18276893
  10. Crosa JH (1989). Genetics and molecular biology of siderophore-mediated iron transport in bacteria. Microbiol. Mol. Biol. Rev. 53, 517– 530. PMC372751 2531838
  11. Das NK, Schwartz AJ, Barthel G, Inohara N, Liu Q, Sankar A, Hill DR, Ma X, Lamberg O, Schnizlein MK, (2020). Microbial Metabolite Signaling Is Required for Systemic Iron Homeostasis. Cell Metab. 31, 115– 130.e6. 31708445 PMC6949377
  12. Dethlefsen L, McFall-Ngai M, and Relman DA (2007). An ecological and evolutionary perspective on human–microbe mutualism and disease. Nature 449, 811– 818. 17943117 PMC9464033
  13. Dogan B, Suzuki H, Herlekar D, Sartor RB, Campbell BJ, Roberts CL, Stewart K, Scherl EJ, Araz Y, Bitar PP, (2014). Inflammation-associated Adherent-invasive Escherichia coli Are Enriched in Pathways for Use of Propanediol and Iron and M-cell Translocation. Inflamm. Bowel Dis. 20, 1919– 1932. 25230163
  14. Ferrante M, Declerck S, De Hertogh G, Van Assche G, Geboes K, Rutgeerts P, Penninckx F, Vermeire S, and D’Hoore A (2008). Outcome after proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis. Inflamm. Bowel Dis. 14, 20– 28. 17973304
  15. Flo TH, Smith KD, Sato S, Rodriguez DJ, Holmes MA, Strong RK, Akira S, and Aderem A (2004). Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature 432, 917– 921. 15531878
  16. Gionchetti P, Calafiore A, Riso D, Liguori G, Calabrese C, Vitali G, Laureti S, Poggioli G, Campieri M, and Rizzello F (2012). The role of antibiotics and probiotics in pouchitis. Ann. Gastroenterol. 25, 100– 105. 24714229 PMC3959382
  17. Gottschick C, Deng Z-L, Vital M, Masur C, Abels C, Pieper DH, and Wagner-Dobler I (2017). The urinary microbiota of men and women and its changes in women during bacterial vaginosis and antibiotic treatment. Microbiome 5, 99. 28807017 PMC5554977
  18. Haas H, Petrik M, and Decristoforo C (2015). An Iron-Mimicking, Trojan Horse-Entering Fungi—Has the Time Come for Molecular Imaging of Fungal Infections? PLoS Pathog. 11. PMC4310729 25634225
  19. Hentze MW, Muckenthaler MU, Galy B, and Camaschella C (2010). Two to Tango: Regulation of Mammalian Iron Metabolism. Cell 142, 24– 38. 20603012
  20. Holden VI, Breen P, Houle S, Dozois CM, and Bachman MA (2016). Klebsiella pneumoniae Siderophores Induce Inflammation, Bacterial Dissemination, and HIF-1α Stabilization during Pneumonia. MBio 7. PMC5021805 27624128
  21. Huttenhower C, Gevers D, Knight R, Abubucker S, Badger JH, Chinwalla AT, Creasy HH, Earl AM, FitzGerald MG, Fulton RS, (2012). Structure, function and diversity of the healthy human microbiome. Nature 486, 207– 214. 22699609 PMC3564958
  22. Jaeggi T, Kortman GAM, Moretti D, Chassard C, Holding P, Dostal A, Boekhorst J, Timmerman HM, Swinkels DW, Tjalsma H, (2015). Iron fortification adversely affects the gut microbiome, increases pathogen abundance and induces intestinal inflammation in Kenyan infants. Gut 64, 731– 742. 25143342
  23. Jarosik GP, Land CB, Duhon P, Chandler R, and Mercer T (1998). Acquisition of Iron by Gardnerella vaginalis. Infect. Immun. 66, 5041– 5047. 9746616 PMC108627
  24. Krewulak KD, and Vogel HJ (2008). Structural biology of bacterial iron uptake. Biochim Biophys Acta Biomembr 1778, 1781– 1804. 17916327
  25. Kruzel ML, Zimecki M, and Actor JK (2017). Lactoferrin in a Context of Inflammation-Induced Pathology. Front. Immunol. 8, 1438. 29163511 PMC5681489
  26. Lee T, Clavel T, Smirnov K, Schmidt A, Lagkouvardos I, Walker A, Lucio M, Michalke B, Schmitt-Kopplin P, Fedorak R, (2017). Oral versus intravenous iron replacement therapy distinctly alters the gut microbiota and metabolome in patients with IBD. Gut 66, 863– 871. 26848182 PMC5531225
  27. Levay PF, and Viljoen M (1995). Lactoferrin: a general review. Haematologica 80, 252– 267. 7672721
  28. Lieu PT, Heiskala M, Peterson PA, and Yang Y (2001). The roles of iron in health and disease. Mol. Aspects Med. 22, 1– 87. 11207374
  29. Liu Z, Ren Z, Zhang J, Chuang C-C, Kandaswamy E, Zhou T, and Zuo L (2018). Role of ROS and Nutritional Antioxidants in Human Diseases. Front. Physiol. 9, 477. 29867535 PMC5966868
  30. Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, and Knight R (2012). Diversity, stability and resilience of the human gut microbiota. Nature 489, 220– 230. 22972295 PMC3577372
  31. Machiels K, Sabino J, Vandermosten L, Joossens M, Arijs I, Bruyn M. de, Eeckhaut V, Assche GV, Ferrante M, Verhaegen J, (2017). Specific members of the predominant gut microbiota predict pouchitis following colectomy and IPAA in UC. Gut 66, 79– 88. 26423113
  32. Mike LA, Smith SN, Sumner CA, Eaton KA, and Mobley HLT (2016). Siderophore vaccine conjugates protect against uropathogenic Escherichia coli urinary tract infection. Proc. Natl. Acad. Sci. 113, 13468– 13473. 27821778 PMC5127358
  33. Mimura T, Rizzello F, Helwig U, Poggioli G, Schreiber S, Talbot IC, Nicholls RJ, Gionchetti P, Campieri M, and Kamm MA (2004). Once daily high dose probiotic therapy (VSL#3) for maintaining remission in recurrent or refractory pouchitis. Gut 53, 108– 114. 14684584 PMC1773918
  34. Minandri F, Imperi F, Frangipani E, Bonchi C, Visaggio D, Facchini M, Pasquali P, Bragonzi A, and Visca P (2016). Role of Iron Uptake Systems in Pseudomonas aeruginosa Virulence and Airway Infection. Infect. Immun. 84, 2324– 2335. 27271740 PMC4962624
  35. Moschen AR, Gerner RR, Wang J, Klepsch V, Adolph TE, Reider SJ, Hackl H, Pfister A, Schilling J, Moser PL, (2016). Lipocalin 2 Protects from Inflammation and Tumorigenesis Associated with Gut Microbiota Alterations. Cell Host Microbe 19, 455– 469. 27078067
  36. Neumann W, Sassone-Corsi M, Raffatellu M, and Nolan EM (2018). Esterase-Catalyzed Siderophore Hydrolysis Activates an Enterobactin-Ciprofloxacin Conjugate and Confers Targeted Antibacterial Activity. J. Am. Chem. Soc. 140, 5193– 5201. 29578687 PMC5921047
  37. Nielsen OH, Soendergaard C, Vikner ME, and Weiss G (2018). Rational Management of Iron-Deficiency Anaemia in Inflammatory Bowel Disease. Nutrients 10, 82. PMC5793310 29342861
  38. Noinaj N, Guillier M, Barnard TJ, and Buchanan SK (2010). TonB-dependent transporters: regulation, structure, and function. Annu. Rev. Microbiol. 64, 43– 60. 20420522 PMC3108441
  39. Pereira FC, and Berry D (2017). Microbial nutrient niches in the gut. Environ. Microbiol. 19, 1366– 1378. 28035742 PMC5412925
  40. Petrik M, Zhai C, Haas H, and Decristoforo C (2017). Siderophores for molecular imaging applications. Clin. Transl. Imaging 5, 15– 27. 28138436 PMC5269471
  41. Qi B, and Han M (2018). Microbial Siderophore Enterobactin Promotes Mitochondrial Iron Uptake and Development of the Host via Interaction with ATP Synthase. Cell 175, 571– 582.e11. 30146159
  42. Runyen-Janecky LJ (2013). Role and regulation of heme iron acquisition in gram-negative pathogens. Front. Cell. Infect. Microbiol. 3. PMC3792355 24116354
  43. Sánchez L, Calvo M, and Brock JH (1992). Biological role of lactoferrin. Arch. Dis. Child. 67, 657– 661. 1599309 PMC1793702
  44. Sassone-Corsi M, and Raffatellu M (2015). No Vacancy: How Beneficial Microbes Cooperate with Immunity To Provide Colonization Resistance to Pathogens. J. Immunol. 194, 4081– 4087. 25888704 PMC4402713
  45. Sassone-Corsi M, Nuccio S-P, Liu H, Hernandez D, Vu C, Takahashi ASA, Edwards RA, and Raffatellu M (2016b). Microcins mediate competition among Enterobacteriaceae in the inflamed gut. In Nature, p. PMC5145735 27798599
  46. Shaler CR, Elhenawy W, and Coombes BK (2019). The Unique Lifestyle of Crohn’s Disease-Associated Adherent-Invasive Escherichia coli. J. Mol. Biol. 431, 2970– 2981. 31029703
  47. Sipponen T, Savilahti E, Kolho K-L, Nuutinen H, Turunen U, and Fárkkilá M (2008). Crohn’s disease activity assessed by fecal calprotectin and lactoferrin: correlation with Crohn’s disease activity index and endoscopic findings. Inflamm. Bowel Dis. 14, 40– 46. 18022866
  48. Steigedal M, Marstad A, Haug M, Damas JK, Strong RK, Roberts PL, Himpsl SD, Stapleton A, Hooton TM, Mobley HLT, (2014). Lipocalin 2 Imparts Selective Pressure on Bacterial Growth in the Bladder and Is Elevated in Women with Urinary Tract Infection. J. Immunol. Author Choice 193, 6081– 6089. PMC4258450 25398327
  49. Tyrrell J, and Callaghan M (2016). Iron acquisition in the cystic fibrosis lung and potential for novel therapeutic strategies. Microbiology 162, 191– 205. 26643057 PMC4772740
  50. Vasil ML, and Ochsner UA (1999). The response of Pseudomonas aeruginosa to iron: genetics, biochemistry and virulence. Mol. Microbiol. 34, 399– 413. 10564483
  51. Vega-Bautista A, de la Garza M, Carrero JC, Campos-Rodríguez R, Godínez-Victoria M, and Drago-Serrano ME (2019). The Impact of Lactoferrin on the Growth of Intestinal Inhabitant Bacteria. Int. J. Mol. Sci. 20, 4101. PMC6801499 31547574
  52. Vonaesch P, Anderson M, and Sansonetti PJ (2018). Pathogens, microbiome and the host: emergence of the ecological Koch’s postulates. FEMS Microbiol. Rev. 42, 273– 292. 29325027
  53. Wang J, Lonergan ZR, Gonzalez-Gutierrez G, Nairn BL, Maxwell CN, Zhang Y, Andreini C, Karty JA, Chazin WJ, Trinidad JC, (2019). Multi-metal restriction by calprotectin impacts de novo flavin biosynthesis in Acinetobacter baumannii. Cell Chem. Biol. 26, 745– 755.e7. 30905682 PMC6525019
  54. Ward PP, and Conneely OM (2004). Lactoferrin: Role in iron homeostasis and host defense against microbial infection. Biometals 17, 203– 208. 15222466
  55. Weinberg ED (1978). Iron and infection. Microbiol. Rev. 42, 45– 66. 379572 PMC281418
  56. Werner T, Wagner SJ, Martínez I, Walter J, Chang J-S, Clavel T, Kisling S, Schuemann K, and Haller D (2011). Depletion of luminal iron alters the gut microbiota and prevents Crohn’s disease-like ileitis. Gut 60, 325– 333. 21076126
  57. Winkelmann G (2007). Ecology of siderophores with special reference to the fungi. BioMetals 20, 379. 17235665
  58. Wolfe AJ, and Brubaker L (2019). Urobiome updates: advances in urinary microbiome research. Nat. Rev. Urol. 16, 73– 74. 30510275 PMC6628711
  59. Zhu W, Winter MG, Spiga L, Hughes ER, Chanin R, Mulgaonkar A, Pennington J, Maas M, Behrendt CL, Kim J, (2020). Xenosiderophore Utilization Promotes Bacteroides thetaiotaomicron Resilience during Colitis. Cell Host Microbe 27, 376– 388.e8. 32075741 PMC7439322
  60. Zollner A, Schmiderer A, Reider SJ, Oberhuber G, Pfister A, Texler B, Watschinger C, Koch R, Effenberger M, Raine T, (2020). Fecal biomarkers in inflammatory bowel diseases: calprotectin versus lipocalin-2 - a comparative study. J. Crohns Colitis. 32556317
  61. Zygiel EM, Nelson CE, Brewer LK, Oglesby-Sherrouse AG, and Nolan EM (2019). The human innate immune protein calprotectin induces iron starvation responses in Pseudomonas aeruginosa. J. Biol. Chem. 294, 3549– 3562. 30622135 PMC6416435

Cited by

Sorted by citations

Authors
Gerner, R. R., Nuccio, S.-P., & Raffatellu, M.
Affiliations
  • Innsbruck Medical University (AT)
  • University of California San Diego (US)
  • Chiba University (JP)
Corresponding author
Raffatellu, Manuela
ORCID
Venue
Molecular Aspects of Medicine
Publisher
Elsevier BV
Published
2020-10
Volume
75
Pages
100895
ISSN
0098-2997 (ISSN-L)
DOI
10.1016/j.mam.2020.100895
PMC
PMC7554189
OpenAlex
W3082170247
Cited by
45
References
26
Citations by year
2026: 7 · 2025: 10 · 2024: 9 · 2023: 7 · 2022: 5 · 2021: 7
FWCI
0.74
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Aspects of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • Burroughs Wellcome Fund
  • Max Kade Foundation
  • Crohn's and Colitis Foundation
Topics
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords
iron, host-microbe interactions, iron limitation, mucosal surfaces, commensal microorganisms, pathogenic bacteria, antimicrobial defense, metalloproteins, respiratory tract, gastrointestinal tract
MeSH terms
Animals, Humans, Iron

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review