Nramp1 and Other Transporters Involved in Metal Withholding during Infection

Wessling-Resnick, Marianne

doi:10.1074/jbc.r115.643973

Cited by 136Iron Metabolism and DisordersTrace Elements in HealthBacterial Genetics and Biotechnology

Nramp1 and Other Transporters Involved in Metal Withholding during Infection

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Wessling-Resnick, Marianne·2015·Journal of Biological Chemistry

DOI 10.1074/jbc.r115.643973PMC PMC4521020

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Abstract

During the course of infection, many natural defenses are set up along the boundaries of the host-pathogen interface. Key among these is the host response to withhold metals to restrict the growth of invading microbes. This simple act of nutritional warfare, starving the invader of an essential element, is an effective means of limiting infection. The physiology of metal withholding is often referred to as "nutritional immunity," and the mechanisms of metal transport that contribute to this host response are the focus of this review.

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For intracellular pathogens including Mycobacterium tuberculosis and Salmonella enterica subsp. enterica serovar Typhimurium, NRAMP reduces metal availability by redirecting storage of cellular Fe, Mn and magnesium from the phagolysosome to the cytoplasm.
“For intracellular pathogens including Mycobacterium tuberculosis and Salmonella enterica subsp. enterica serovar Typhimurium, NRAMP reduces metal availability by redirecting storage of cellular Fe, Mn and magnesium from the phagolysosome to the cytoplasm 17-19 .”
From Nutritional immunity: the battle for nutrient metals at the host–pathogen interface (2022) · cites this paper as [19]
The “Iron and Manganese Transport” section (page unavailable) says Nramp1 may restrict pathogen growth by moving essential metals out of phagosomes, and the paper links it to resistance against Mycobacteria and Salmonella. But it describes the direction of Nramp1 transport as unsettled and does not identify magnesium as a metal moved by this mechanism; the claim presents both as established. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Most studies have shown that Nramp1 shifts iron and other divalent cations from the phagolysosome to the cytosol.
“Most studies have shown that Nramp1 shifts iron and other divalent cations from the phagolysosome to the cytosol.”
From “Pumping iron”—how macrophages handle iron at the systemic, microenvironmental, and cellular levels (2017) · cites this paper as [249]
The weight of evidence now indicates that Nramp1 transports iron and manganese out of the phagocytic vacuole into the cytoplasm, depleting the phagosome of these essential metals.
“The weight of the evidence now indicates that Nramp1 transports iron and manganese out of the phagocytic vacuole into the cytoplasm [46], thereby depleting the phagosome of these essential metals.”
From Iron and infection (2018) · cites this paper as [46]
NRAMP1 is a divalent metal ion transporter expressed on the membranes of phagolysosomes of phagocytic cells.
“Another crucial host defence strategy lies on the expression of the natural resistance‐associated macrophage protein 1 (NRAMP1, or SLC11A1), a divalent metal ion transporter expressed on the membranes of phagolysosomes of phagocytic cells. 110”
From The battle for iron in enteric infections (2020) · cites this paper as [110]
Nramp1 depletes the phagosome of manganese and, to a lesser extent, iron.
“In response to infection, neutrophils and macrophages express the natural resistance–associated macrophage protein 1 (Nramp1), which depletes the phagosome of manganese and, to a lesser extent, iron (67, 142).”
From Transition Metals and Virulence in Bacteria (2016) · cites this paper as [142]

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Authors: Wessling-Resnick, M.
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2015-07
Volume: 290
Issue: 31
Pages: 18984-18990
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.r115.643973
PMC: PMC4521020
OpenAlex: W1952983243
Cited by: 136
References: 101
Citations by year: 2026: 13 · 2025: 6 · 2024: 10 · 2023: 15 · 2022: 8 · 2021: 17 · 2020: 10 · 2019: 18 · 2018: 16 · 2017: 12 · 2016: 9 · 2015: 2
FWCI: 1.94
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 1889 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (R01ES0146380, R01DK064570)
Topics: Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords: NRAMP1, metal transporters, nutritional immunity, host-pathogen interface, host defense against infection, iron transport, host-pathogen interaction
MeSH terms: Natural Resistance-associated Macrophage Protein 1, Animals, Bacterial Infections, Biological Transport, Homeostasis, Humans, Immunity, Innate, Iron, Manganese, Cation Transport Proteins, Host-Pathogen Interactions

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Nramp1 and Other Transporters Involved in Metal Withholding during Infection

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