Evidence map›Paper›PMID 25686372›Full record

ArticleNature chemical biology2015

Compounds targeting disulfide bond forming enzyme DsbB of Gram-negative bacteria.

Cristina Landeta, Jessica L Blazyk, Feras Hatahet, Brian M Meehan, Markus Eser, Alissa Myrick, Ludmila Bronstain, Shoko Minami, Holly Arnold, Na Ke and 6 more

Abstract read
In one paragraph

Article in Nature chemical biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
–field-weighted citation impact
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

35 citing papers in PubMed.

  1. Article
  2. Article
  3. Disulphide bond-forming enzymes in clostridial species.Microbiology (Reading, England) · 2025
    Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Distinct enzymatic strategies forCritical reviews in biochemistry and molecular biology · 2023
    Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Smart Flow Electrosynthesis and Application of Organodisulfides in Redox Flow Batteries.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022
    Article
  18. Article
  19. Anti-Virulence Therapeutic Approaches forAntibiotics (Basel, Switzerland) · 2021
    Review
  20. Article
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

16 authors.

Cristina LandetaDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
Jessica L BlazykDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
Feras HatahetDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
Brian M MeehanDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
Markus EserDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
Alissa MyrickDepartment of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA.
Ludmila BronstainDivision of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
Shoko MinamiDepartment of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA.
Holly ArnoldDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
Na KeDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
Eric J RubinDepartment of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA.
Barbara C FurieDivision of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
Bruce FurieDivision of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
Jon BeckwithDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
Rachel DuttonDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
Dana BoydDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.

Funding

Treatments for Nipah Virus InfectionU54AI057159 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WHELAN, SEAN PJ · 2003 to 2013
$113.7M
HARVARD CLINICAL AND TRANSLATIONAL SCIENCE CENTER (UL1)UL1RR025758 · NCRR · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2008 to 2011
$91.4M
PROGRAM IN BLOOD COAGULATION AND VASCULAR BIOLOGYT32HL007917 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI Robert C Flaumenhaft · 1999 to 2026
$11.1M
Translational Research Skills DevelopmentU54HL112302 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI FURIE, BRUCE · 2012 to 2016
$11.1M
Thrombus Formation In VivoP01HL087203 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI FURIE, BRUCE · 2008 to 2012
$8.8M
Target IdentificationP01AI074805 · NIAID · FLORIDA STATE UNIVERSITY · PI CROSS, TIMOTHY A · 2009 to 2013
$8.7M
Microbial Diversity in Mechanisms of Disulfide Bond Formation and ReductionR01GM041883 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI BOYD, DANA · 1989 to 2014
$7.8M
IMMUNOLOGY AND INFECTIOUS DISEASES IN PUBLIC HEALTHT32AI007638 · NIAID · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI RUBIN, ERIC J. · 2000 to 2014
$2.2M
Thiol Isomerases During Thrombus FormationR01HL092125 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI FURIE, BARBARA C · 2009 to 2013
$2.2M
NCRR NIH HHS 5-UL1RR02568-01NCRR NIH HHS UL1 RR025758NHLBI NIH HHS P01 HL087203NHLBI NIH HHS P01-HL087203NHLBI NIH HHS R01 HL092125NHLBI NIH HHS R01-HL092125NHLBI NIH HHS T32 HL007917NHLBI NIH HHS T32-HL07917NHLBI NIH HHS U54 HL112302NIAID NIH HHS 3P01-AI074805-04S1NIAID NIH HHS P01 AI074805NIAID NIH HHS T32 AI007638NIAID NIH HHS U54 AI057159NIAID NIH HHS U54-AI057159NIGMS NIH HHS GM041883NIGMS NIH HHS R01 GM041883
6 · The paper itself

Abstract

In bacteria, disulfide bonds confer stability on many proteins exported to the cell envelope or beyond. These proteins include numerous bacterial virulence factors, and thus bacterial enzymes that promote disulfide bond formation represent targets for compounds inhibiting bacterial virulence. Here, we describe a new target- and cell-based screening methodology for identifying compounds that inhibit the disulfide bond-forming enzymes Escherichia coli DsbB (EcDsbB) or Mycobacterium tuberculosis VKOR (MtbVKOR), which can replace EcDsbB, although the two are not homologs. Initial screening of 51,487 compounds yielded six specifically inhibiting EcDsbB. These compounds share a structural motif and do not inhibit MtbVKOR. A medicinal chemistry approach led us to select related compounds, some of which are much more effective DsbB inhibitors than those found in the screen. These compounds inhibit purified DsbB and prevent anaerobic growth of E. coli. Furthermore, these compounds inhibit all but one of the DsbBs of nine other Gram-negative pathogenic bacteria tested.

Indexed as

AgarAnti-Bacterial AgentsBacterial ProteinsCatalytic DomainChemistry, PharmaceuticalCombinatorial Chemistry TechniquesDisulfidesDose-Response Relationship, DrugDrug DesignElectron TransportEscherichia coliEscherichia coli ProteinsMass SpectrometryMembrane ProteinsMicrobial Sensitivity TestsMycobacterium smegmatisAgarAnti-Bacterial AgentsBacterial ProteinsDisulfidesdsbA protein, E coliDsbB protein, BacteriaEscherichia coli ProteinsMembrane ProteinsProtein Disulfide-Isomerases

Identifiers

PMID25686372
PMCPMC4366281

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Registered trials

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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.