Protective role of bacillithiol in superoxide stress and Fe–S metabolism in Bacillus subtilis
Open accessAbstract
Glutathione (GSH) serves as the prime thiol in most organisms as its depletion increases antibiotic and metal toxicity, impairs oxidative stress responses, and affects Fe and Fe-S cluster metabolism. Many gram-positive bacteria lack GSH, but instead produce other structurally unrelated yet functionally equivalent thiols. Among those, bacillithiol (BSH) has been recently identified in several low G+C gram-positive bacteria. In this work, we have explored the link between BSH and Fe-S metabolism in Bacillus subtilis. We have identified that B. subtilis lacking BSH is more sensitive to oxidative stress (paraquat), and metal toxicity (Cu(I) and Cd(II)), but not H2 O2 . Furthermore, a slow growth phenotype of BSH null strain in minimal medium was observed, which could be recovered upon the addition of selected amino acids (Leu/Ile and Glu/Gln), supplementation of iron, or chemical complementation with BSH disulfide (BSSB) to the growth medium. Interestingly, Fe-S cluster containing isopropylmalate isomerase (LeuCD) and glutamate synthase (GOGAT) showed decreased activities in BSH null strain. Deficiency of BSH also resulted in decreased levels of intracellular Fe accompanied by increased levels of manganese and altered expression levels of Fe-S cluster biosynthetic SUF components. Together, this study is the first to establish a link between BSH and Fe-S metabolism in B. subtilis.
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In B. subtilis, bacillithiol is important for the synthesis of FeS proteins.
“In B. subtilis, bacillithiol (BSH)145 is important for the synthesis of FeS proteins.146,147”
From Metals in Motion: Understanding Labile Metal Pools in Bacteria (2025) · cites this paper as [146]
The Discussion (page unavailable) says reduced Fe–S enzyme activity in BSH-deficient B. subtilis indicates *potential* involvement of BSH in de novo Fe–S cluster biosynthesis. The Results section “BSH and Fe–S biosynthesis” also reports lower levels of the biosynthetic components SufC and SufB in the mutant. These findings support a link, but do not establish that BSH is important for the synthesis of Fe–S proteins themselves. (LLM, conf=0.84)
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Andrews, S. C., Robinson, A. K., & Rodríguez-Quiñones, F. (2003) · FEMS Microbiology Reviews · doi:10.1016/s0168-6445(03)00055-x · Cited by 2,702 · see citing works
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Metals in Motion: Understanding Labile Metal Pools in Bacteria
Helmann, J. D. (2025) · Biochemistry · doi:10.1021/acs.biochem.4c00726 · Cited by 49 · see citing works
- Authors
- Fang, Z., & Dos Santos, P. C.
- Affiliations
- Wake Forest University (US)
- Department of Chemistry Wake Forest University Winston‐Salem North Carolina 27016
- Venue
- MicrobiologyOpen
- Publisher
- Wiley
- Published
- 2015-05-18
- Volume
- 4
- Issue
- 4
- Pages
- 616-631
- ISSN
- 2045-8827 (ISSN-L)
- PMC
- PMC4554457
- OpenAlex
- W1693453083
- Cited by
- 38
- References
- 1
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 4 · 2020: 4 · 2019: 3 · 2018: 5 · 2017: 4 · 2016: 2 · 2015: 1
- FWCI
- 1.58
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- MicrobiologyOpen (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (MCB-1054623)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
- Keywords
- bacillithiol, Bacillus subtilis, superoxide stress, oxidative stress, metal toxicity, copper toxicity, cadmium toxicity, paraquat sensitivity, thiol metabolism, glutamate synthase, manganese accumulation, amino acid supplementation, chemical complementation
- MeSH terms
- Antioxidants, Bacillus subtilis, Cadmium, Copper, Culture Media, Cysteine, Glucosamine, Hydrogen Peroxide, Iron, Iron-Sulfur Proteins, Paraquat, Sulfur, Superoxides, Oxidative Stress
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