ArticleThe Journal of biological chemistry2012
Discovery of intracellular heme-binding protein HrtR, which controls heme efflux by the conserved HrtB-HrtA transporter in Lactococcus lactis.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 91 citations in OpenAlex.
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- Biosensors for Detection of Labile Heme in Biological Samples.Biosensors · 2025Review
- Heme in Bacterial Pathogenesis and as an Antimicrobial Target.Chemical reviews · 2025Review
- The Vicious Circle of Metabolic Dysfunction-Associated Steatotic Liver Disease When Micronutrient Deficiency Drives Microbial Imbalance and Liver Injury.Life (Basel, Switzerland) · 2025Review
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- DNA-bound structure of Clostridioides difficile heme-sensing HsmR gives insight on how the unique dimer mode governs DNA specificity in MarR transcriptional regulators.Nucleic acids research · 2025Article
- High-yield porphyrin production through metabolic engineering and biocatalysis.Nature biotechnology · 2025Article
- Engineering coupled consortia-based biosensors for diagnostic.Nature communications · 2025Article
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- HssS activation by membrane heme defines a paradigm for two-component system signaling inmBio · 2024Article
- Proximity-based defensive mutualism between Streptomyces and Mesorhizobium by sharing and sequestering iron.The ISME journal · 2024Article
- Structures of the DarR transcription regulator reveal unique modes of second messenger and DNA binding.Nature communications · 2023Article
- Heme acquisition and tolerance in Gram-positive model bacteria: An orchestrated balance.Heliyon · 2023Review
- Applications of the Whole-Cell System in the Efficient Biosynthesis of Heme.International journal of molecular sciences · 2023Review
- Whole-Cell P450 Biocatalysis Using Engineered Escherichia coli with Fine-Tuned Heme Biosynthesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Two functionally distinct heme/iron transport systems are virulence determinants of the fish pathogenVirulence · 2022Article
- 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
- Sedimentary Cobalt Protoporphyrin as a Potential Precursor of Prosthetic Heme Group for Bacteria Inhabiting Fossil Organic Matter-Rich Shale Rock.Biomolecules · 2021Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Most commensal and food bacteria lack heme biosynthesis genes. For several of these, the capture of environmental heme is a means of activating aerobic respiration metabolism. Our previous studies in the Gram-positive bacterium Lactococcus lactis showed that heme exposure strongly induced expression of a single operon, called here hrtRBA, encoding an ortholog of the conserved membrane hrt (heme-regulated transporter) and a unique transcriptional regulator that we named HrtR. We show that HrtR expressed as a fusion protein is a heme-binding protein. Heme iron interaction with HrtR is non-covalent, hexacoordinated, and involves two histidines, His-72 and His-149. HrtR specifically binds a 15-nt palindromic sequence in the hrtRBA promoter region, which is needed for hrtRBA repression. HrtR-DNA binding is abolished by heme addition, which activates expression of the HrtB-HrtA (HrtBA) transporter in vitro and in vivo. The use of HrtR as an intracellular heme sensor appears to be conserved among numerous commensal bacteria, in contrast with numerous Gram-positive pathogens that use an extracellular heme-sensing system, HssRS, to regulate hrt. Finally, we show for the first time that HrtBA permease controls heme toxicity by its direct and specific efflux. The use of an intracellular heme sensor to control heme efflux constitutes a novel paradigm for bacterial heme homeostasis.
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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.