ArticleInfection and immunity2007
The ChrA-ChrS and HrrA-HrrS signal transduction systems are required for activation of the hmuO promoter and repression of the hemA promoter in Corynebacterium diphtheriae.
Article in Infection and immunity, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 71 citations in OpenAlex.
- Rv3839-Rv3840 links the endogenous heme biosynthesis pathway with Mycobacterium tuberculosis adaptation to nitric oxide and iron limitation stress.PLoS genetics · 2026Article
- Rv3839-Rv3840 links the endogenous heme biosynthesis pathway withbioRxiv : the preprint server for biology · 2026Article
- Porphyrin pathways as targets for combating antimicrobial resistance: virulence and therapeutic opportunities.Frontiers in cellular and infection microbiology · 2026Review
- Heme in Bacterial Pathogenesis and as an Antimicrobial Target.Chemical reviews · 2025Review
- The Exoproteome and Surfaceome of ToxigenicJournal of proteome research · 2025Article
- Regulation of heme biosynthesis via the coproporphyrin dependent pathway in bacteria.Frontiers in microbiology · 2024Review
- Maintenance of heme homeostasis inJournal of bacteriology · 2023Article
- Heme acquisition and tolerance in Gram-positive model bacteria: An orchestrated balance.Heliyon · 2023Review
- Severe anaemia, iron deficiency, and susceptibility to invasive bacterial infections.Wellcome open research · 2023Review
- TheMicrobiology spectrum · 2022Article
- Exogenously Scavenged and Endogenously Synthesized Heme Are Differentially Utilized by Mycobacterium tuberculosis.Microbiology spectrum · 2022Article
- A pseudokinase version of the histidine kinase ChrS promotes high heme tolerance ofFrontiers in microbiology · 2022Article
- The Transcriptional Regulatory Network ofMicroorganisms · 2021Review
- Genetic Regulation of Metal Ion Homeostasis in Staphylococcus aureus.Trends in microbiology · 2020Review
- HrrSA orchestrates a systemic response to heme and determines prioritization of terminal cytochrome oxidase expression.Nucleic acids research · 2020Article
- Transcriptome profile of Corynebacterium pseudotuberculosis in response to iron limitation.BMC genomics · 2019Article
- Toxic but tasty - temporal dynamics and network architecture of heme-responsive two-component signaling in Corynebacterium glutamicum.Molecular microbiology · 2019Article
- Article
- From Host Heme To Iron: The Expanding Spectrum of Heme Degrading Enzymes Used by Pathogenic Bacteria.Frontiers in cellular and infection microbiology · 2018Review
- Membrane Topology and Heme Binding of the Histidine Kinases HrrS and ChrS inFrontiers in microbiology · 2018Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transcription of the Corynebacterium diphtheriae hmuO gene, which encodes a heme oxygenase involved in heme iron utilization, is activated in a heme- or hemoglobin-dependent manner in part by the two-component system ChrA-ChrS. Mutation of either the chrA or the chrS gene resulted in a marked reduction of hemoglobin-dependent activation at the hmuO promoter in C. diphtheriae; however, it was observed that significant levels of hemoglobin-dependent expression were maintained in the mutants, suggesting that an additional activator is involved in regulation. A BLAST search of the C. diphtheriae genome sequence revealed a second two-component system, encoded by DIP2268 and DIP2267, that shares similarity with ChrS and ChrA, respectively; we have designated these genes hrrS (DIP2268) and hrrA (DIP2267). Analysis of hmuO promoter expression demonstrated that hemoglobin-dependent activity was fully abolished in strains from which both the chrA-chrS and the hrrA-hrrS two-component systems were deleted. Similarly, deletion of the sensor kinase genes chrS and hrrS or the genes encoding both of the response regulators chrA and hrrA also eliminated hemoglobin-dependent activation at the hmuO promoter. We also show that the regulators ChrA-ChrS and HrrA-HrrS are involved in the hemoglobin-dependent repression of the promoter upstream of hemA, which encodes a heme biosynthesis enzyme. Evidence for cross talk between the ChrA-ChrS and HrrA-HrrS systems is presented. In conclusion, these findings demonstrate that the ChrA-ChrS and HrrA-HrrS regulatory systems are critical for full hemoglobin-dependent activation at the hmuO promoter and also suggest that these two-component systems are involved in the complex mechanism of the regulation of heme homeostasis in C. diphtheriae.
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