ArticleProceedings of the National Academy of Sciences of the United States of America2013
Activation of heme biosynthesis by a small molecule that is toxic to fermenting Staphylococcus aureus.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- Metabolic reprogramming promotesMicrobiology (Reading, England) · 2026Article
- Heme in Bacterial Pathogenesis and as an Antimicrobial Target.Chemical reviews · 2025Review
- Article
- HssS activation by membrane heme defines a paradigm for two-component system signaling inmBio · 2024Article
- Maintenance of heme homeostasis inJournal of bacteriology · 2023Article
- Applications of the Whole-Cell System in the Efficient Biosynthesis of Heme.International journal of molecular sciences · 2023Review
- DnaJ and ClpX Are Required for HitRS and HssRS Two-Component System Signaling in Bacillus anthracis.Infection and immunity · 2022Article
- Simultaneous Exposure to Intracellular and Extracellular Photosensitizers for the Treatment of Staphylococcus aureus Infections.Antimicrobial agents and chemotherapy · 2021Article
- The Multifaceted Bacterial Cysteine Desulfurases: From Metabolism to Pathogenesis.Antioxidants (Basel, Switzerland) · 2021Review
- Broad Spectrum Antibiotic Xanthocillin X Effectively KillsACS central science · 2021Article
- Directed evolution reveals the mechanism of HitRS signaling transduction in Bacillus anthracis.PLoS pathogens · 2020Article
- Biology of antimicrobial resistance and approaches to combat it.Science translational medicine · 2020Review
- Host nutrient milieu drives an essential role for aspartate biosynthesis during invasiveProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Comprehensive analysis of iron utilization by Mycobacterium tuberculosis.PLoS pathogens · 2020Article
- Computational advances in combating colloidal aggregation in drug discovery.Nature chemistry · 2019Review
- Fur regulation of Staphylococcus aureus heme oxygenases is required for heme homeostasis.International journal of medical microbiology : IJMM · 2018Article
- Article
- A quinolinol-based small molecule with anti-MRSA activity that targets bacterial membrane and promotes fermentative metabolism.The Journal of antibiotics · 2017Article
- Antibacterial photosensitization through activation of coproporphyrinogen oxidase.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Visualization of the role of host heme on the virulence of the heme auxotroph Streptococcus agalactiae.Scientific reports · 2017Article
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Authors and funding
14 authors.
Funding
Abstract
Staphylococcus aureus is a significant infectious threat to global public health. Acquisition or synthesis of heme is required for S. aureus to capture energy through respiration, but an excess of this critical cofactor is toxic to bacteria. S. aureus employs the heme sensor system (HssRS) to overcome heme toxicity; however, the mechanism of heme sensing is not defined. Here, we describe the identification of a small molecule activator of HssRS that induces endogenous heme biosynthesis by perturbing central metabolism. This molecule is toxic to fermenting S. aureus, including clinically relevant small colony variants. The utility of targeting fermenting bacteria is exemplified by the fact that this compound prevents the emergence of antibiotic resistance, enhances phagocyte killing, and reduces S. aureus pathogenesis. Not only is this small molecule a powerful tool for studying bacterial heme biosynthesis and central metabolism; it also establishes targeting of fermentation as a viable antibacterial strategy.
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