ArticleMolecular microbiology2012
Menaquinone biosynthesis potentiates haem toxicity in Staphylococcus aureus.
Article in Molecular microbiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 89 citations in OpenAlex.
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- Ferric reductase related proteins Frp1 and Frp2 mediate reductive heme uptake in the opportunistic pathogen Candida albicans.Journal of inorganic biochemistry · 2026Article
- Biosensors for Detection of Labile Heme in Biological Samples.Biosensors · 2025Review
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- Metals in Motion: Understanding Labile Metal Pools in Bacteria.Biochemistry · 2025Review
- Mechanisms ofmBio · 2024Article
- Heme acquisition and tolerance in Gram-positive model bacteria: An orchestrated balance.Heliyon · 2023Review
- Allosteric inhibition ofPhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Article
- Experimental Validation of MHC Class I and II Peptide-Based Potential Vaccine Candidates for Human Papilloma Virus Using Sprague-Dawly Models.Molecules (Basel, Switzerland) · 2023Article
- Structural basis for heme detoxification by an ATP-binding cassette-type efflux pump in gram-positive pathogenic bacteria.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Host Polyunsaturated Fatty Acids Potentiate Aminoglycoside Killing of Staphylococcus aureus.Microbiology spectrum · 2022Article
- Comparative Studies to Uncover Mechanisms of Action ofACS infectious diseases · 2022Article
- Article
- Iron restriction induces the small-colony variant phenotype inFrontiers in microbiology · 2022Article
- Identification of structurally diverse menaquinone-binding antibiotics with in vivo activity against multidrug-resistant pathogens.Nature microbiology · 2022Article
- Analysis and Reconstitution of the Menaquinone Biosynthesis Pathway inMicroorganisms · 2021Article
- Structure, Assembly, and Function of Tripartite Efflux and Type 1 Secretion Systems in Gram-Negative Bacteria.Chemical reviews · 2021Review
6 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 2 countries.
Funding
Abstract
Staphylococcus aureus is a pathogen that infects multiple anatomical sites leading to a diverse array of diseases. Although vertebrates can restrict the growth of invading pathogens by sequestering iron within haem, S. aureus surmounts this challenge by employing high-affinity haem uptake systems. However, the presence of excess haem is highly toxic, necessitating tight regulation of haem levels. To overcome haem stress, S. aureus expresses the detoxification system HrtAB. In this work, a transposon screen was performed in the background of a haem-susceptible, HrtAB-deficient S. aureus strain to identify the substrate transported by this putative pump and the source of haem toxicity. While a recent report indicates that HrtAB exports haem itself, the haem-resistant mutants uncovered by the transposon selection enabled us to elucidate the cellular factors contributing to haem toxicity. All mutants identified in this screen inactivated the menaquinone (MK) biosynthesis pathway. Deletion of the final steps of this pathway revealed that quinone molecules localizing to the cell membrane potentiate haem-associated superoxide production and subsequent oxidative damage. These data suggest a model in which membrane-associated haem and quinone molecules form a redox cycle that continuously generates semiquinones and reduced haem, both of which react with atmospheric oxygen to produce superoxide.
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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.