ArticleThe Journal of biological chemistry2022
A newly identified flavoprotein disulfide reductase Har protects Streptococcus pneumoniae against hypothiocyanous acid.
Article in The Journal of biological chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Implications of bacterial exposure to reactive oxygen and chlorine species.Infection and immunity · 2026Review
- Determinants of susceptibility and tolerance ofInfection and immunity · 2026Review
- Factors governing the response ofFrontiers in cellular and infection microbiology · 2026Review
- A Defined Artificial Saliva Medium Allows Characterization of the Hypothiocyanite Response of Streptococcus sanguinis and Streptococcus mutans.Molecular oral microbiology · 2025Article
- Genome-wide characterization of hypothiocyanite stress response inJournal of bacteriology · 2025Article
- The role of metals in hypothiocyanite resistance inJournal of bacteriology · 2024Article
- The therapeutic potential of thiocyanate and hypothiocyanous acid against pulmonary infections.Free radical biology & medicine · 2024Review
- The role of metals in hypothiocyanite resistance inbioRxiv : the preprint server for biology · 2024Article
- Expression of RcrB confers resistance to hypochlorous acid in uropathogenicJournal of bacteriology · 2023Article
- Identification ofJournal of bacteriology · 2023Article
- Substrate-dependent metabolomic signatures of myeloperoxidase activity in airway epithelial cells: Implications for early cystic fibrosis lung disease.Free radical biology & medicine · 2023Article
- Expression of RcrB confers resistance to hypochlorous acid in uropathogenicbioRxiv : the preprint server for biology · 2023Article
- A Year at the Forefront of Bacterial Defense Systems Against Neutrophilic Oxidants.Biology open · 2023Article
- Hypothiocyanite and host-microbe interactions.Molecular microbiology · 2023Article
- The oxidative stress response ofFrontiers in microbiology · 2023Review
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypothiocyanous acid (HOSCN) is an antimicrobial oxidant produced from hydrogen peroxide and thiocyanate anions by heme peroxidases in secretory fluids such as in the human respiratory tract. Some respiratory tract pathogens display tolerance to this oxidant, which suggests that there might be therapeutic value in targeting HOSCN defense mechanisms. However, surprisingly little is known about how bacteria protect themselves from HOSCN. We hypothesized that tolerant pathogens have a flavoprotein disulfide reductase that uses NAD(P)H to directly reduce HOSCN, similar to thioredoxin reductase in mammalian cells. Here, we report the discovery of a previously uncharacterized flavoprotein disulfide reductase with HOSCN reductase activity, which we term Har (hypothiocyanous acid reductase), in Streptococcus pneumoniae, a bacterium previously found to be tolerant of HOSCN. S. pneumoniae generates large amounts of hydrogen peroxide that can be converted to HOSCN in the respiratory tract. Using deletion mutants, we demonstrate that the HOSCN reductase is dispensable for growth of S. pneumoniae in the presence of lactoperoxidase and thiocyanate. However, bacterial growth in the HOSCN-generating system was completely crippled when deletion of HOSCN reductase activity was combined with disruption of GSH import or recycling. Our findings identify a new bacterial HOSCN reductase and demonstrate a role for this protein in combination with GSH utilization to protect S. pneumoniae from HOSCN.
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