Function and Mechanism of Action of Dictyostelium Nramp1 (Slc11a1) in Bacterial Infection
Open accessAbstract
Dictyostelium amoebae are professional phagocytes, which ingest bacteria as the principal source of food. We have cloned the Dictyostelium homologue of human natural resistance-associated membrane protein 1 (Nramp1) [solute carrier family 11 member 1 (Slc11a1)], an endo-lysosomal membrane protein that confers on macrophages resistance to infection by a variety of intracellular bacteria and protozoa. The Dictyostelium Nramp1 gene encodes a protein of 53 kDa with 11 putative transmembrane domains. The Nramp1 gene is transcribed during the growth-phase and downregulated to barely detectable levels upon starvation. To gain insights into their intracellular localization, we fused Nramp1 or the vatB subunit of the V-H(+)ATPase with green fluorescent protein and expressed in cells. Green fluorescent protein-vatB was inserted in membranes of all acidic compartments and the contractile vacuole network and decorated macropinosomes and phagosomes. Green fluorescent protein-Nramp1 decorated macropinosomes and phagosomes, in addition to intracellular vesicular compartments positive for endosomal SNARE protein Vti1 or vacuolin, a marker of the exocytic pathway. Nramp1 disruption generated mutants that were more permissive hosts than wild-type cells for intracellular growth of Legionella pneumophila and Micobacterium avium. Nramp1 overexpression protected cells from L. pneumophila infection. Evidence is provided that Nramp1 transports metal cations out of the phagolysosome in an ATP-dependent process and that L. pneumophila and M. avium use different mechanisms to neutralize Nramp1 activity.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Several bacterial pathogens for humans, such as legionella, mycobacteria and salmonella, are pathogenic also for Dictyostelium.
“Several bacterial pathogens for humans, such as legionella, mycobacteria and salmonella, are pathogenic also for Dictyostelium, favouring the use of this model to study host-pathogen interactions [9-19].”
From Genome-wide transcriptional changes induced by phagocytosis or growth on bacteria in Dictyostelium (2008) · cites this paper as [16]
V-H+ ATPase, Rab7 and calreticulin are typical markers of phagosomal traffic, whereas gp24, discoidin II and gp130 are extracellular or membrane proteins that could be entrapped in the phagosome.
“The V-H+ ATPase, Rab7 and calreticulin are typical markers of phagosomal traffic [16,81-83], whereas gp24, discoidin II and gp130 are extracellular or membrane proteins that could be entrapped in the phagosome.”
From Genome-wide transcriptional changes induced by phagocytosis or growth on bacteria in Dictyostelium (2008) · cites this paper as [16]
Cites
Cloning and characterization of a mammalian proton-coupled metal-ion transporter
Gunshin, H., Mackenzie, B., Berger, U. V., Gunshin, Y., Romero, M. F., Boron, W. F., Nussberger, S., Gollan, J. L., & Hediger, M. A. (1997) · Nature · doi:10.1038/41343 · Cited by 3,166 · see citing works
Maniak, M., Rauchenberger, R., Albrecht, R., Murphy, J., & Gerisch, G. (1995) · Cell · doi:10.1016/0092-8674(95)90207-4 · Cited by 354 · see citing works
Supek, F., Supekova, L., Nelson, H., & Nelson, N. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.10.5105 · Cited by 325 · see citing works
Forbes, J. R., & Gros, P. (2003) · Blood · doi:10.1182/blood-2003-02-0425 · Cited by 288 · see citing works
Solomon, J. M., Rupper, A., Cardelli, J. A., & Isberg, R. R. (2000) · Infection and Immunity · doi:10.1128/iai.68.5.2939-2947.2000 · Cited by 215 · see citing works
Hagele, S., Kohler, R., Merkert, H., Schleicher, M., Hacker, J., & Steinert, M. (2000) · Cellular Microbiology · doi:10.1046/j.1462-5822.2000.00044.x · Cited by 198 · see citing works
Self-citationBlackwell, J. M., Searle, S., Mohamed, H., & White, J. K. (2003) · Immunology Letters · doi:10.1016/s0165-2478(02)00231-6 · Cited by 169 · see citing works
Role of Iron in<i>Nramp1</i>-Mediated Inhibition of Mycobacterial Growth
Zwilling, B. S., Kuhn, D. E., Wikoff, L., Brown, D., & Lafuse, W. (1999) · Infection and Immunity · doi:10.1128/iai.67.3.1386-1392.1999 · Cited by 155 · see citing works
Understanding the multiple functions of Nramp1
Blackwell, J. M., Searle, S., Goswami, T., & Miller, E. N. (2000) · Microbes and Infection · doi:10.1016/s1286-4579(00)00295-1 · Cited by 136 · see citing works
Kuhn, D. E., Baker, B. D., Lafuse, W. P., & Zwilling, B. S. (1999) · Journal of Leukocyte Biology · doi:10.1002/jlb.66.1.113 · Cited by 113 · see citing works
Kuhn, D. E., Lafuse, W. P., & Zwilling, B. S. (2001) · Journal of Leukocyte Biology · doi:10.1189/jlb.69.1.43 · Cited by 79 · see citing works
Fajardo, M., Schleicher, M., Noegel, A., Bozzaro, S., Killinger, S., Heuner, K., Hacker, J., & Steinert, M. (2004) · Microbiology · doi:10.1099/mic.0.27111-0 · Cited by 73 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Nutritional immunity beyond iron: a role for manganese and zinc
Kehl-Fie, T. E., & Skaar, E. P. (2010) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2009.11.008 · Cited by 634 · see citing works
The phagosome: compartment with a license to kill
Haas, A. (2007) · Traffic · doi:10.1111/j.1600-0854.2006.00531.x · Cited by 450 · see citing works
Hoffmann, C., Finsel, I., Otto, A., Pfaffinger, G., Rothmeier, E., Hecker, M., Becher, D., & Hilbi, H. (2014) · Cellular Microbiology · doi:10.1111/cmi.12256 · Cited by 126 · see citing works
Mortensen, B. L., & Skaar, E. P. (2013) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2013.00095 · Cited by 99 · see citing works
Genome-wide transcriptional changes induced by phagocytosis or growth on bacteria in Dictyostelium
Sillo, A., Bloomfield, G., Balest, A., Balbo, A., Pergolizzi, B., Peracino, B., Skelton, J., Ivens, A., & Bozzaro, S. (2008) · BMC Genomics · doi:10.1186/1471-2164-9-291 · Cited by 69 · see citing works
Self-citationWithholding iron as a cellular defence mechanism – friend or foe?
Collins, H. L. (2008) · European Journal of Immunology · doi:10.1002/eji.200838505 · Cited by 59 · see citing works
(2012) · Current Topics in Membranes · doi:10.1016/b978-0-12-394390-3.00010-0 · Cited by 47 · see citing works
Animal models in tuberculosis research – where is the beef?
Myllymäki, H., Niskanen, M., Oksanen, K. E., & Rämet, M. (2015) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2015.1049529 · Cited by 44 · see citing works
Competition for Manganese at the Host–Pathogen Interface
Kelliher, J. L., & Kehl-Fie, T. E. (2016) · Progress in Molecular Biology and Translational Science · doi:10.1016/bs.pmbts.2016.05.002 · Cited by 34 · see citing works
Nramp1 and NrampB Contribute to Resistance against Francisella in Dictyostelium
Brenz, Y., Ohnezeit, D., Winther-Larsen, H. C., & Hagedorn, M. (2017) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2017.00282 · Cited by 19 · see citing works
Iron acquisition by Mycobacterium tuberculosis residing within myeloid dendritic cells
Olakanmi, O., Kesavalu, B., Abdalla, M. Y., & Britigan, B. E. (2013) · Microbial Pathogenesis · doi:10.1016/j.micpath.2013.09.002 · Cited by 17 · see citing works
- Authors
- Peracino, B., Wagner, C., Balest, A., Balbo, A., Pergolizzi, B., Noegel, A. A., Steinert, M., & Bozzaro, S.
- Affiliations
- University of Turin (IT)
- University of Würzburg (DE)
- Ospedale San Luigi Gonzaga (IT)
- University of Cologne (DE)
- Corresponding author
- Bozzaro, Salvatore
- ORCID
- Venue
- Traffic
- Publisher
- Wiley
- Published
- 2005-11-09
- Volume
- 7
- Issue
- 1
- Pages
- 22-38
- ISSN
- 1398-9219 (ISSN-L)
- 1600-0854
- OpenAlex
- W1484672918
- Cited by
- 96
- References
- 12
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 4 · 2020: 2 · 2019: 3 · 2018: 4 · 2017: 7 · 2016: 6 · 2015: 2 · 2014: 5 · 2013: 13 · 2012: 4
- FWCI
- 3.85
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Traffic (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
- Funders
- Deutsche Forschungsgemeinschaft
- Russian Science Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Legionella and Acanthamoeba research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- Dictyostelium, NRAMP1, SLC11A1, V-ATPase, phagolysosomes, Legionella pneumophila, Mycobacterium avium, intracellular bacterial infection, metal ion transport, phagosome, macropinosomes
- MeSH terms
- Natural Resistance-associated Macrophage Protein 1, Amino Acid Sequence, Animals, Bacteria, Cell Line, Cell Membrane, Cloning, Molecular, Dictyostelium, Escherichia coli, Gene Expression Regulation, Humans, Iron, Legionella, Lysosomes, Molecular Sequence Data, Mycobacterium avium, Phagocytosis, Phagosomes, Sequence Alignment, Cation Transport Proteins, Green Fluorescent Proteins
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
