Dysregulation of Magnesium Transport Protects Bacillus subtilis against Manganese and Cobalt Intoxication
Open accessAbstract
Cellular metal ion homeostasis is tightly regulated. When metal ion levels are imbalanced, or when one metal is at toxic levels, enzymes may bind to the wrong metal cofactor. Enzyme mismetallation can impair metabolism, lead to new and deleterious reactions, and cause cell death. Beginning with Bacillus subtilis strains genetically sensitized to metal intoxication through loss of efflux or by lowering intracellular iron, we identified mutations that suppress the deleterious effects of excess Mn(II) or Co(II). For both metals, mutations in mpfA , encoding a Mg(II) efflux pump, suppressed toxicity. These mutant strains have elevated intracellular Mg(II), suggesting that Mg(II)-dependent processes are very sensitive to disruption by transition metals.
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Prior to osmotic upshift, mpfA cells have approximately 36% increased intracellular Mg2+ levels.
“We noted that prior to osmotic upshift, mpfA cells have ∼36% increased intracellular Mg2+ levels (see Table S3 in the supplemental material), consistent with the ∼50% increase noted previously (5).”
From A Central Role for Magnesium Homeostasis during Adaptation to Osmotic Stress (2022) · cites this paper as [5]
MpfA is now appreciated as a Mg2+ efflux pump in both B. subtilis and S. aureus.
“MpfA is now appreciated as a Mg2+ efflux pump in both B. subtilis and S. aureus (5, 63).”
From A Central Role for Magnesium Homeostasis during Adaptation to Osmotic Stress (2022) · cites this paper as [5]
B. subtilis encodes four MpfA paralogs, all with salt-responsive transcriptional regulation.
“Interestingly, B. subtilis encodes four MpfA paralogs (5), all with salt-responsive transcriptional regulation (64).”
From A Central Role for Magnesium Homeostasis during Adaptation to Osmotic Stress (2022) · cites this paper as [5]
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King, A., Horigian, P., & Eswara, P. J. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.08.31.748404
- Authors
- Pi, H., Wendel, B. M., & Helmann, J. D.
- Affiliations
- Cornell University (US)
- Venue
- Journal of Bacteriology
- Publisher
- American Society for Microbiology
- Published
- 2020-03-11
- Volume
- 202
- Issue
- 7
- ISSN
- 0021-9193 (ISSN-L)
- 1098-5530
- PMC
- PMC7167470
- OpenAlex
- W3002278267
- Cited by
- 35
- References
- 71
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 2 · 2022: 14 · 2021: 4 · 2020: 2
- FWCI
- 3.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Bacteriology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | National Institutes of Health (R35GM122461)
- 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
- Health Sciences › Nursing › Nutrition and Dietetics › Magnesium in Health and Disease
- Keywords
- magnesium transport, manganese toxicity, cobalt toxicity, metal homeostasis, suppressor mutations, intracellular magnesium, Bacillus subtilis
- MeSH terms
- Adaptation, Biological, Bacillus subtilis, Bacterial Proteins, Biological Transport, Cobalt, Iron, Magnesium, Manganese, Models, Biological, Operon, Gene Expression Regulation, Bacterial
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