Evidence map›Paper›PMID 35952759›Full record

ArticleThe Journal of biological chemistry2022

A newly identified flavoprotein disulfide reductase Har protects Streptococcus pneumoniae against hypothiocyanous acid.

Heather L Shearer, Paul E Pace, James C Paton, Mark B Hampton, Nina Dickerhof

Open access · goldAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.6field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 19 citations in OpenAlex.

  1. Review
  2. Review
  3. Factors governing the response ofFrontiers in cellular and infection microbiology · 2026
    Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. The role of metals in hypothiocyanite resistance inbioRxiv : the preprint server for biology · 2024
    Article
  9. Article
  10. Identification ofJournal of bacteriology · 2023
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. The oxidative stress response ofFrontiers in microbiology · 2023
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 2 countries.

Heather L ShearerDepartment of Pathology and Biomedical Science, Centre for Free Radical Research, University of Otago Christchurch, Christchurch, New Zealand.
Paul E PaceDepartment of Pathology and Biomedical Science, Centre for Free Radical Research, University of Otago Christchurch, Christchurch, New Zealand.
James C PatonDepartment of Molecular and Biomedical Science, Research Centre for Infectious Diseases, University of Adelaide, Adelaide, Australia.
Mark B HamptonDepartment of Pathology and Biomedical Science, Centre for Free Radical Research, University of Otago Christchurch, Christchurch, New Zealand.
Nina DickerhofDepartment of Pathology and Biomedical Science, Centre for Free Radical Research, University of Otago Christchurch, Christchurch, New Zealand. Electronic address: nina.dickerhof@otago.ac.nz.
University of Otago · NZThe University of Adelaide · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Anti-Infective AgentsThiocyanatesAnimalsDisulfidesHemeHumansHydrogen PeroxideLactoperoxidaseMammalsNADOxidantsStreptococcus pneumoniaeThioredoxin-Disulfide ReductaseAnti-Infective AgentsDisulfidesHemeHydrogen Peroxidehypothiocyanous acidLactoperoxidaseNADOxidantsthiocyanateThiocyanatesThioredoxin-Disulfide Reductaseflavoprotein disulfide reductasehypothiocyanous acidlactoperoxidasemyeloperoxidasepneumoniapyridine nucleotide-disulfide reductaseSPD_1415thioredoxin reductase

Identifiers

PMID35952759
PMCPMC9483559
OpenAlexW4290703693

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.