Replication of Neisseria meningitidis within Epithelial Cells Requires TonB-Dependent Acquisition of Host Cell Iron
Open accessAbstract
Neisseria meningitidis (meningococcus [MC]) is able to enter and replicate within epithelial cells. Iron, an essential nutrient for nearly all organisms, is an important determinant in the ability of MC to cause disease; however, its role in MC intracellular replication has not been investigated. We analyzed the growth of MC within the A431 human epithelial cell line and the dependence of this growth on iron uptake. We present evidence here that chelation of iron from infected tissue culture cells with Desferal strongly inhibited intracellular replication of wild-type (wt) MC. We also provide genetic evidence that iron must be acquired by MC from the host cell in order for it to replicate. An hmbR mutant that is unable to use hemoglobin iron and could not grow in tissue culture media without iron supplementation replicated more rapidly within epithelial cells than its wt parent strain. An fbpA mutant that is unable to utilize human transferrin iron or lactoferrin iron replicated normally within cells. In contrast, a tonB mutant could not replicate intracellularly unless infected cultures were supplemented with ferric nitrate. Taken together, these findings strongly suggest that MC intracellular replication requires TonB-dependent uptake of a novel host cell iron source.
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
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?
Once secreted, siderophores capture ferric iron in the microenvironment, and iron-siderophore complexes are transferred into the periplasm via TonB-dependent receptors and subsequently imported to the cytoplasm by ABC transporters.
“Once secreted, siderophores capture ferric iron in the microenvironment and ironsiderophore complexes are transferred into the periplasm via TonBdependent receptors and subsequently imported to the cytoplasm by ABC transporters (Larson et al., 2002).”
From Iron in infection and immunity (2020) · cites this paper as Larson et al., 2002
The paper describes siderophores as secreted ferric-iron chelators that deliver iron through siderophore receptors, and says uptake through the receptors it discusses requires TonB (Abstract; page not provided). It does not describe iron–siderophore complexes moving into the periplasm or their subsequent import into the cytoplasm by ABC transporters. Its account of a periplasmic iron-binding protein and inner-membrane transporter concerns transferrin and lactoferrin iron, not siderophores. (LLM, conf=0.86)
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.
The citation lists haven’t been fetched yet
References 32 · Cited by 46
Research works printed but not linked: 1
- [1]Al-Younes, H. M., T. Rudel, V. Brinkmann, A. J. Szczepek, and T. F. Meyer. 2001. Low iron availability modulates the course of Chlamydia pneumoniae infection. Cell Microbiol. 3:427-437. [DOI] [PubMed] [Google Scholar]
- Authors
- Larson, J. A., Higashi, D. L., Stojiljkovic, I., & So, M.
- Affiliations
- Oregon Health & Science University (US)
- Department of Microbiology and Immunology, Emory University, Atlanta, Georgia 30322
- Corresponding author
- Larson, Jason A.
- ORCID
- So, Magdalene
- Venue
- Infection and Immunity
- Publisher
- American Society for Microbiology
- Published
- 2002-03
- Volume
- 70
- Issue
- 3
- Pages
- 1461-1467
- ISSN
- 0019-9567 (ISSN-L)
- 1098-5522
- PMC
- PMC127810
- OpenAlex
- W2153614857
- Cited by
- 46
- References
- 32
- Citations by year
- 2025: 1 · 2022: 2 · 2020: 2 · 2019: 1 · 2017: 2 · 2015: 3 · 2014: 1 · 2013: 2 · 2012: 2
- FWCI
- 3.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Infection and Immunity (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (AI 32493, R01AI032493)
- Topics
- Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
- 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
- Neisseria meningitidis, intracellular replication, epithelial cells, iron chelation, transferrin, lactoferrin, hemoglobin, A431 cells, bacterial virulence
- MeSH terms
- Bacterial Proteins, Biological Transport, Cells, Cultured, Cervix Uteri, Culture Media, Epithelial Cells, Female, Ferric Compounds, Humans, Iron, Iron Chelating Agents, Membrane Proteins, Mutation, Neisseria meningitidis, Nitrates, Transferrin
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
