407: SLC11A2 withholds metals from Salmonella in the gut epithelium

Norberg ES et al., Proceedings of the National Academy of Sciences - Using metal‑responsive fluorescent Salmonella reporters, calf intestinal loops, and CRISPR edited epithelial cells, this study shows that the divalent metal transporter SLC11A2 is recruited to Salmonella‑containing vacuoles and restricts Fe2+ and Mn2+, limiting intracellular bacterial replication. Key terms: SLC11A2, nutritional immunity, Salmonella enterica, iron and manganese, intestinal epithelium.

Study Highlights:
The authors used metal‑sensing GFP reporters in Salmonella and a calf ligated ileal loop model to map metal availability and found a subpopulation of bacteria in IECs and lamina propria cells exposed to ≤0.1 µM Fe2+ and Zn2+, and possibly Mn2+, early in infection. SLC11A2 localized to the apical surface and endosomal network of IECs and was recruited to maturing Salmonella‑containing vacuoles; CRISPR knockout of SLC11A2 in HCT116 epithelial cells increased bacterial replication. Fluorescent reporters and ICP‑MS indicate vacuolar STm are less starved for Fe2+ and Mn2+ in the absence of SLC11A2, while Zn2+ and Mg2+ sensing was unchanged. Salmonella counters SLC11A2‑mediated restriction through the Mn2+/Fe2+ transporter MntH and siderophore production.

Conclusion:
SLC11A2 mediates epithelial nutritional immunity by sequestering Fe2+ and Mn2+ in Salmonella‑containing vacuoles, reducing vacuolar metal availability and limiting intracellular Salmonella replication.

Music:
Enjoy the music based on this article at the end of the episode.

Article title:
SLC11A2 withholds divalent metals from
Salmonella
in the gut epithelium

First author:
Norberg ES

Journal:
Proceedings of the National Academy of Sciences

DOI:
10.1073/pnas.2532675123

Reference:
Norberg ES, Knodler LA, et al. SLC11A2 withholds divalent metals from Salmonella in the gut epithelium. PNAS. 2026;123:e2532675123. doi:10.1073/pnas.2532675123

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

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Episode link: https://basebybase.com/episodes/slc11a2-withholds-divalent-metals-from-salmonella

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-07-05.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited transcript sections covering nutritional immunity concepts, IEC-localized SLC11A2 function, calf ileal loop in vivo model, metal-responsive STm reporters, SLC11A2 recruitment to SCVs, SLC11A2 knockout effects in HCT116 cells, bacterial countermeasures (MntH and siderophores), intracellular niches (SCV vs cytoso
- transcript topics: Nutritional immunity and trace metal tug-of-war; SLC11A2 (NRAMP2) in intestinal epithelial cells; Calf ligated ileal loop model and metal availability; Metal-responsive Salmonella reporters (iroN, sitA, zinT); SLC11A2 recruitment to Salmonella-containing vacuoles; SLC11A2 knockout in HCT116 cells and impact on Salmonella replication

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 6
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- SLC11A2 is recruited to Salmonella-containing vacuoles (SCV) in intestinal epithelial cells and restricts Fe2+ and Mn2+ availability within SCVs, limiting intracellular Salmonella
- Deletion of SLC11A2 in HCT116 cells increases Salmonella replication intracellularly, notably at 8 and 16 hours post-infection in 1% fetal calf serum conditions.
- Salmonella counteracts SLC11A2 through MntH and siderophores; entC deletion reduces replication in WT and complementation rescues replication, indicating competition for Fe2+/Mn2+
- Metal-reporter data show early metal starvation in a subpopulation of intracellular Salmonella (≈38% Zn2+-limited at 2 h; regional shifts by 8 h toward lamina propria).
- Calf ligated ileal loop model demonstrates metal restriction at IECs and lamina propria during acute infection.
- SLC11A2 knockout reduces ferritin (FTH1/FTL) levels in cells, suggesting reduced cytosolic iron availability.

QC result: Pass.