The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Iron and infection: the heart of the matter
Open accessAbstract
Bacterial resistance to antibiotics is a major threat to clinical medicine. However, natural resistance to bacterial infection, which does not depend on antibiotics, is a powerful protective mechanism common to all mankind. The availability of iron is the heart of the matter and the successful functioning of these antibacterial systems depends entirely upon an extremely low level of free ionic iron (10(-18) M) in normal tissue fluids. This in turn depends on well-oxygenated tissues where the oxidation-reduction potential (Eh) and pH control the binding of iron by unsaturated transferrin and lactoferrin. Bacterial virulence is greatly enhanced by freely available iron, such as that in fully-saturated transferrin or free haemoglobin. Following trauma a fall in tissue Eh and pH due to ischaemia, plus the reducing powers of bacteria, can make iron in transferrin freely available and abolish the bactericidal properties of tissue fluids with disastrous results for the host. Hyperbaric oxygen is a possible therapeutic measure that could restore normal bactericidal systems in infected tissues by raising the Eh and pH.
Overview
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.
Integrity signals
Registry
Cites
Statistics
Verification
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.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Hence, the understanding of the uptake pathways for FeEnt and FeGEnt and their degradation products has clinical importance related to their correlations with microbial virulence (47,48).”
From Siderophore-mediated iron acquisition by Klebsiella pneumoniae (2024) · cites this paper as [48]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Supplemental Perioperative Oxygen to Reduce the Incidence of Surgical-Wound Infection
Greif, R. T., Akça, O., Horn, E.-P., Kurz, A. M., & Sessler, D. I. (2000) · New England Journal of Medicine · doi:10.1056/nejm200001203420303 · Cited by 1,151
Vancomycin-Resistant Enterococcal Infections
Murray, B. E. (2000) · New England Journal of Medicine · doi:10.1056/nejm200003093421007 · Cited by 894
Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor
Wood, A. J. J., Lieschke, G. J., & Burgess, A. W. (1992) · New England Journal of Medicine · doi:10.1056/nejm199207023270106 · Cited by 811
The virulence of Staphylococcus pyogenes for man; a study of the problems of wound infection.
Elek, S. D., & Conen, P. E. (1957) · PubMed · Cited by 654
Wound Tissue Oxygen Tension Predicts the Risk of Wound Infection in Surgical Patients
Hopf, H. W. (1997) · Archives of Surgery · doi:10.1001/archsurg.1997.01430330063010 · Cited by 637
Role of Iron in Bacterial Infection
Bullen, J. J., Rogers, H. J., & Griffiths, E. (1978) · Modern aspects of electrochemistry · doi:10.1007/978-3-642-66956-9_1 · Cited by 494
Self-citationSloan, E. P. (1999) · JAMA · doi:10.1001/jama.282.19.1857 · Cited by 459
The virulence of staph pyogenes for man : a study of wound infection
Sd, E. (1957) · Medical Entomology and Zoology · Cited by 389
Role of iron in the pathogenesis of Vibrio vulnificus infections
Wright, A. C., Simpson, L. M., & Oliver, J. D. (1981) · Infection and Immunity · doi:10.1128/iai.34.2.503-507.1981 · Cited by 343
Bactericidal Activity of Aerobic and Anaerobic Polymorphonuclear Neutrophils
Mandell, G. L. (1974) · Infection and Immunity · doi:10.1128/iai.9.2.337-341.1974 · Cited by 331
Liu, C., & Chambers, H. F. “. (2003) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.47.10.3040-3045.2003 · Cited by 319
Fever and Reduced Iron: Their Interaction as a Host Defense Response to Bacterial Infection
Kluger, M. J., & Rothenburg, B. A. (1979) · Science · doi:10.1126/science.760197 · Cited by 265
Iron and infection: molecular, physiological and clinical aspects.
Bullen, J. J., & Griffiths, E. (1999) · Cited by 244
Self-citationColony-Stimulating Factors for the Management of Neutropenia in Cancer Patients
Dale, D. C. (2002) · Drugs · doi:10.2165/00003495-200262001-00001 · Cited by 192
Simmen, H., & Blaser, J. (1993) · The American Journal of Surgery · doi:10.1016/s0002-9610(05)80576-8 · Cited by 178
Oxidation-Reduction Potentials in Bacteriology and Biochemistry.
(1931) · JAMA · doi:10.1001/jama.1931.02730100055044 · Cited by 148
ASSOCIATION BETWEEN BLOOD TRANSFUSION AND INFECTION IN INJURED PATIENTS
Edna, T., & Bjerkeset, T. (1992) · The Journal of Trauma: Injury, Infection, and Critical Care · doi:10.1097/00005373-199211000-00010 · Cited by 115
Debrunner, P. G. (1983) · Science · doi:10.1126/science.220.4603.1266 · Cited by 110
The effect of iron compounds on the virulence of Escherichia coli for guinea-pigs.
Bullen, J. J., Leigh, L. C., & Rogers, H. J. (1968) · PubMed · Cited by 108
Self-citationElevated Serum Iron, Low Unbound Transferrin and Candidiasis in Acute Leukemia
Caroline, L., Rosner, F., & Kozinn, P. J. (1969) · Blood · doi:10.1182/blood.v34.4.441.441 · Cited by 97
Halliwell, B. B., Aruoma, O. I., Mufti, G. J., & Bomford, A. B. (1988) · FEBS Letters · doi:10.1016/0014-5793(88)81061-5 · Cited by 90
The Role of Iron in Nonspecific Resistance to Infection Induced by Endotoxin
Elin, R. J., & Wolff, S. M. (1974) · The Journal of Immunology · doi:10.4049/jimmunol.112.2.737 · Cited by 80
Bullen, J. J., Griffiths, E., & Edmiston, C. E. (1999) · Shock · doi:10.1097/00024382-199911000-00013 · Cited by 70
Self-citationThe enhancement of bacterial infections by adrenaline.
EVANS, D. G., Miles, A. A., & Niven, J. S. F. (1948) · PubMed · Cited by 69
OXIDATION‐REDUCTION POTENTIALS IN BACTERIOLOGY AND BIOCHEMISTRY
(1950) · The Medical Journal of Australia · doi:10.5694/j.1326-5377.1950.tb81013.x · Cited by 66
Haemoglobin-based blood substitutes and sepsis
Griffiths, E., Cortes, A., Gilbert, N., Stevenson, P., MacDonald, S. L., & Pepper, D. S. (1995) · The Lancet · doi:10.1016/s0140-6736(95)90168-x · Cited by 59
The effect of passage and iron on the virulence of Pseudomonas aeruginosa
Forsberg, C. M., & Bullen, J. J. (1972) · Journal of Clinical Pathology · doi:10.1136/jcp.25.1.65 · Cited by 55
Self-citationThe Effects of Francisella Tularensis Infection on Iron Metabolism in Man
Pekarek, R. S., Bostian, K. A., Bartelloni, P. J., Calia, F. M., & Beisel, W. R. (1969) · The American Journal of the Medical Sciences · doi:10.1097/00000441-196907000-00003 · Cited by 53
Rogers, H. J. (1967) · PubMed · Cited by 52
Self-citationThe Value of Adjuvant Treatment in Young Women with Breast Cancer
Clive, S., & Dixon, J. M. (2002) · Drugs · doi:10.2165/00003495-200262010-00001 · Cited by 35
Karp, J. E., & Merz, W. G. (1986) · Journal of Clinical Oncology · doi:10.1200/jco.1986.4.2.216 · Cited by 35
Infection after injury: association with blood transfusion.
Rosemurgy, A. S., Hart, M., Murphy, C., ALBRINK, M. H., Piazza, A., Leparc, G. F., & Harris, R. E. (1992) · PubMed · Cited by 30
Measurement of human plasma hemoglobin by difference spectrophotometry.
Rd, L., Swerdlow, F., & Mr, G. (1971) · PubMed · Cited by 20
Increased non‐transferrin bound iron in plasma‐depleted SAG‐M red blood cell units
Marwah, S., Blann, A. D., Harrison, P., Lumley, M. A., Wright, J., McDowell, J., Phillips, J. D., Rea, C. A., & Bareford, D. (2002) · Vox Sanguinis · doi:10.1046/j.1423-0410.2002.00153.x · Cited by 19
The role of Eh, pH and iron in the bactericidal power of human plasma
Bullen, J., Spalding, P. B., Ward, C. G., & Rogers, H. J. (1992) · FEMS Microbiology Letters · doi:10.1016/0378-1097(92)90581-8 · Cited by 15
Self-citationThe role of Eh, pH and iron in the bactericidal power of human plasma
Bullen, J. J., Spalding, P. B., Ward, C., & Rogers, H. J. (1992) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.1992.tb05287.x · Cited by 13
Self-citation[The problem of antibiotic resistance].
Presinger, M. (1956) · PubMed · Cited by 8
Research works printed but not linked: 3
- [14] Griffiths, E., Williams, P. (1999) The iron-uptake systems of pathogenic bacteria, fungi, and protozoa. In: Iron and Infection. Molecular, Physiological, and Clinical aspects (Bullen, J.J., Griffiths, E., Eds.), pp.87â212 Wiley, Chichester.
- [31] Ward, C.G., Bullen, J.J. (1999) Clinical and physiological aspects. In: Iron and Infection. Molecular, Physiological, and Clinical Aspects (Bullen, J.J., Griffiths, E., Eds.), pp.369â450 Wiley, Chichester. · DOI
- [33] Hewitt, L.F. (1950) Oxidationâreduction potentials in bacteriology and biochemistry. 6th ed., E&S Livingstone, Edinburgh, pp. 97â127.
Cited by
Sorted by citations
Kaneko, Y., Thoendel, M., Olakanmi, O., Britigan, B. E., & Singh, P. K. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30783 · Cited by 672
Riordan, T. (2007) · Clinical Microbiology Reviews · doi:10.1128/cmr.00011-07 · Cited by 563
Kell, D. B. (2009) · BMC Medical Genomics · doi:10.1186/1755-8794-2-2 · Cited by 554
Hod, E. A., Zhang, N., Sokol, S. A., Wojczyk, B. S., Francis, R. O., Ansaldi, D., Francis, K. P., Della-Latta, P., Whittier, S., Sheth, S., et al. (2010) · Blood · doi:10.1182/blood-2009-10-245001 · Cited by 485
FDA report: Ferumoxytol for intravenous iron therapy in adult patients with chronic kidney disease
Lu, M., Cohen, M. H., Rieves, D., & Pazdur, R. (2010) · American Journal of Hematology · doi:10.1002/ajh.21656 · Cited by 443
Metadata
- Authors
- Bullen, J. J., Rogers, H. J., Spalding, P. B., & Ward, C. G.
- Affiliations
- University of Miami (US)
- National Institute for Medical Research (GB)
- Corresponding author
- Bullen, John J.
- Venue
- FEMS Immunology & Medical Microbiology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-03
- Volume
- 43
- Issue
- 3
- Pages
- 325-330
- ISSN
- 0928-8244 (ISSN-L)
- 1574-695X
- OpenAlex
- W2047570111
- Cited by
- 273
- References
- 37
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 9 · 2023: 11 · 2022: 10 · 2021: 15 · 2020: 9 · 2019: 15 · 2018: 13 · 2017: 14 · 2016: 12 · 2015: 13 · 2014: 23 · 2013: 20 · 2012: 12
- FWCI
- 1.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- FEMS Immunology & Medical Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Keywords
- iron, bacterial infection, iron acquisition, transferrin, lactoferrin, hemoglobin, redox potential, tissue pH, ischemia, hyperbaric oxygen therapy, innate immunity, bacterial virulence
- MeSH terms
- Animals, Hypoxia, Bacteria, Bacterial Infections, Blood Substitutes, Blood Transfusion, Humans, Hydrogen-Ion Concentration, Hyperbaric Oxygenation, Immunity, Innate, Iron, Leukemia, Oxidation-Reduction, Virulence, Wounds and Injuries, Iron Overload
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