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Cited by 93Bacterial Genetics and BiotechnologyHeavy Metal Exposure and ToxicityFungal and yeast genetics research

Bacillus subtilis MntR coordinates the transcriptional regulation of manganese uptake and efflux systems

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Huang, Xiaojuan, Shin, Jung‐Ho, Pinochet‐Barros, Azul, Su, Tina T., Helmann, John D.·2017·Molecular Microbiology
DOI 10.1111/mmi.13554PMC PMC5218975
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Abstract

Summary: The Bacillus subtilis MntR metalloregulatory protein senses manganese, an essential element required for central metabolism, oxidative stress resistance and replication. An mntR null mutant is highly sensitive to Mn(II) intoxication, which is attributed in part to the constitutive expression of two importers: the proton‐dependent NRAMP family transporter MntH and the ABC transporter MntABCD. Here, we show that an mntR null mutant is still sensitive to Mn(II) intoxication even if both of the import systems are absent. This Mn(II) sensitivity results from the requirement for MntR to activate the transcription of two genes encoding cation diffusion facilitator (CDF) family efflux pumps. Physiological studies indicate that MneP (formerly YdfM) serves as the primary Mn(II) efflux pump with MneS (formerly YeaB) playing a secondary role. Mutant strains lacking mneP are Mn(II) sensitive and accumulate elevated levels of Mn(II), and these effects are exacerbated in a mneP mneS double mutant. DNA‐binding and in vitro transcription studies demonstrate that MntR binds to both the mneP and mneS regulatory regions and directly activates transcription in response to levels of Mn(II) several‐fold higher than required for repression of import genes. These results highlight the delicate balance of Mn(II) uptake and efflux systems controlled by MntR.

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  • Free Mn2+ in the 3 to 6 μM range represents sufficiency, and levels approaching 10 μM represent excess.

    “These analyses suggest that free Mn2+ in the 3 to 6 μM range represents sufficiency (Figure 2), and levels approaching 10 μM represent excess.102”

    From Metals in Motion: Understanding Labile Metal Pools in Bacteria (2025) · cites this paper as [102]

    The Results section on MntR regulation (page unavailable) supports a distinction between Mn(II) sufficiency and elevated Mn(II): uptake repression begins near 0.5 μM external Mn(II), while efflux expression is half-maximal near 50 μM external Mn(II). It does not identify 3–6 μM free Mn²⁺ as sufficient or levels approaching 10 μM free Mn²⁺ as excess; those numerical thresholds and the claim about free rather than external Mn(II) are unsupported. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Best estimates of the labile manganese pool in model bacteria derive from measurements of the amount of free Mn2+ required for regulation of gene expression by Mn2+-dependent regulators such as MntR and Mn2+-dependent riboswitches.

    “Our current best estimates of the labile manganese pool in model bacteria derive from measurements of the amount of free Mn2+ required for regulation of gene expression by Mn2+-dependent regulators such as the MntR transcription factor101,102 and Mn2+-dependent riboswitches.103”

    From Metals in Motion: Understanding Labile Metal Pools in Bacteria (2025) · cites this paper as [102]

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Authors
Huang, X., Shin, J., Pinochet‐Barros, A., Su, T. T., & Helmann, J. D.
Affiliations
Cornell University (US)
Corresponding author
Helmann, John D.
ORCID
Venue
Molecular Microbiology
Publisher
Wiley
Published
2016-11-02
Volume
103
Issue
2
Pages
253-268
ISSN
  • 0950-382X (ISSN-L)
  • 1365-2958
DOI
10.1111/mmi.13554
PMC
PMC5218975
OpenAlex
W2534721040
Cited by
93
References
7
Citations by year
2026: 9 · 2025: 10 · 2024: 13 · 2023: 7 · 2022: 12 · 2021: 10 · 2020: 9 · 2019: 11 · 2018: 7 · 2017: 5
FWCI
5.14
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Molecular Microbiology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of General Medical Sciences (R01GM059323)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords
Bacillus subtilis, MntR, metalloregulatory proteins, manganese homeostasis, manganese efflux, manganese uptake, MntH, multinational corporations, transcriptional regulation, DNA binding
MeSH terms
Bacillus subtilis, Bacterial Proteins, Binding Sites, Manganese, Promoter Regions, Genetic, Repressor Proteins, Transcription, Genetic, Gene Expression Regulation, Bacterial, ATP-Binding Cassette Transporters, Cation Transport Proteins

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