ArticleMolecular microbiology2014
Methylglyoxal resistance in Bacillus subtilis: contributions of bacillithiol-dependent and independent pathways.
Article in Molecular microbiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 76 citations in OpenAlex.
- An Escherichia coli Phosphotransferase System Modulates Methylglyoxal Resistance by Regulating Intracellular Potassium.Molecular microbiology · 2026Article
- A putativeFrontiers in immunology · 2026Article
- Bacterial Adaptation to Stress Induced by Glyoxal/Methylglyoxal and Advanced Glycation End Products.Microorganisms · 2025Review
- Methylglyoxal is an antibacterial effector produced by macrophages during infection.Cell host & microbe · 2025Article
- A Comprehensive Review of Metabolic Dysfunction-Associated Steatotic Liver Disease: Its Mechanistic Development Focusing on Methylglyoxal and Counterbalancing Treatment Strategies.International journal of molecular sciences · 2025Review
- Expanded genome and proteome reallocation in a novel, robustmSystems · 2024Article
- Greedy reduction of Bacillus subtilis genome yields emergent phenotypes of high resistance to a DNA damaging agent and low evolvability.Nucleic acids research · 2023Article
- 3-Phenyllactic Acid and Polyphenols Are Substances Enhancing the Antibacterial Effect of Methylglyoxal in Manuka Honey.Foods (Basel, Switzerland) · 2023Article
- Glyoxalase 2: Towards a Broader View of the Second Player of the Glyoxalase System.Antioxidants (Basel, Switzerland) · 2022Review
- Metabolic Shades of S-D-Lactoylglutathione.Antioxidants (Basel, Switzerland) · 2022Review
- Developing methylotrophic microbial platforms for a methanol-based bioindustry.Frontiers in bioengineering and biotechnology · 2022Review
- The two-Cys-type TetR repressor GbaA confers resistance under disulfide and electrophile stress in Staphylococcus aureus.Free radical biology & medicine · 2021Article
- Listeriolysin S: A bacteriocin fromProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Molecular Mechanisms for Bacterial Potassium Homeostasis.Journal of molecular biology · 2021Review
- Detoxification of methylglyoxal by the glyoxalase system is required for glutathione availability and virulence activation in Listeria monocytogenes.PLoS pathogens · 2021Article
- The Bacillus subtilis monothiol bacilliredoxin BrxC (YtxJ) and the Bdr (YpdA) disulfide reductase reduce S-bacillithiolated proteins.Redox biology · 2021Article
- c-di-AMP, a likely master regulator of bacterial KProceedings of the National Academy of Sciences of the United States of America · 2021Article
- SigB-regulated antioxidant functions in gram-positive bacteria.World journal of microbiology & biotechnology · 2021Review
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Methylglyoxal (MG) is a toxic by-product of glycolysis that damages DNA and proteins ultimately leading to cell death. Protection from MG is often conferred by a glutathione-dependent glyoxalase pathway. However, glutathione is absent from the low-GC Gram-positive Firmicutes, such as Bacillus subtilis. The identification of bacillithiol (BSH) as the major low-molecular-weight thiol in the Firmicutes raises the possibility that BSH is involved in MG detoxification. Here, we demonstrate that MG can rapidly and specifically deplete BSH in cells, and we identify both BSH-dependent and BSH-independent MG resistance pathways. The BSH-dependent pathway utilizes glyoxalase I (GlxA, formerly YwbC) and glyoxalase II (GlxB, formerly YurT) to convert MG to d-lactate. The critical step in this pathway is the activation of the KhtSTU K(+) efflux pump by the S-lactoyl-BSH intermediate, which leads to cytoplasmic acidification. We show that cytoplasmic acidification is both necessary and sufficient for maximal protection from MG. Two additional MG detoxification pathways operate independent of BSH. The first involves three enzymes (YdeA, YraA and YfkM) which are predicted to be homologues of glyoxalase III that converts MG to d-lactate, and the second involves YhdN, previously shown to be a broad specificity aldo-keto reductase that converts MG to acetol.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.