Evidence map›Paper›PMID 26882549›Full record

ArticleEMBO reports2016

Exploiting dominant-negative toxins to combat Staphylococcus aureus pathogenesis.

Tamara Reyes-Robles, Ashira Lubkin, Francis Alonzo, D Borden Lacy, Victor J Torres

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in EMBO reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
5.6field-weighted citation impact, top 4% 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

33 citing papers in PubMed, 59 citations in OpenAlex.

  1. Article
  2. Science advances · 2025
    Article
  3. DisarmingPathogens (Basel, Switzerland) · 2025
    Review
  4. Article
  5. Infection and immunity · 2024
    Article
  6. Article
  7. Microbiology spectrum · 2023
    Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Identification of a domain critical forThe Journal of biological chemistry · 2020
    Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Tamara Reyes-RoblesDepartment of Microbiology, New York University School of Medicine, New York, NY, USA.
Ashira LubkinDepartment of Microbiology, New York University School of Medicine, New York, NY, USA.
Francis AlonzoDepartment of Microbiology, New York University School of Medicine, New York, NY, USA.
D Borden LacyDepartment of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA.
Victor J TorresDepartment of Microbiology, New York University School of Medicine, New York, NY, USA victor.torres@nyumc.org.
New York University · USVanderbilt University · US

Funding

INFECTIOUS DISEASES &BASIC MICROBIOLOGICAL MECHANISMST32AI007180 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI WEISER, JEFFREY NEAL · 1985 to 2022
$8.9M
Mechanistic Studies Of The Staphylococcus aureus LukAB CytotoxinR01AI099394 · NIAID · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Victor J. Torres · 2013 to 2026
$6.1M
Contribution of LukED to Staphylococcus aureus pathobiologyR01AI105129 · NIAID · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI TORRES, VICTOR J. · 2014 to 2023
$4.9M
Non-Leukocidal Roles of Staphylococcus aureus Bi-component toxins in PathogenesisF30AI124606 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI LUBKIN, ASHIRA LEAH · 2016 to 2019
$155k
Molecular and Cellular Basis of Toxin Mediated Pathogenesis in Staphylococcus aurF32AI098395 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ALONZO, FRANCIS · 2012 to 2013
$94k
Staphylococcus aureus mediated targeting and killing of immune cellsF31AI112290 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI REYES-ROBLES, TAMARA · 2014 to 2015
$62k
NIAID NIH HHS F30 AI124606NIAID NIH HHS F31 AI112290NIAID NIH HHS F32 AI098395NIAID NIH HHS R01 AI099394NIAID NIH HHS R01 AI105129NIAID NIH HHS T32 AI007180
6 · The paper itself

Abstract

Staphylococcus aureus (S. aureus) is a human pathogen that relies on the subversion of host phagocytes to support its pathogenic lifestyle. S. aureus strains can produce up to five beta-barrel, bi-component, pore-forming leukocidins that target and kill host phagocytes. Thus, preventing immune cell killing by these toxins is likely to boost host immunity. Here, we describe the identification of glycine-rich motifs within the membrane-penetrating stem domains of the leukocidin subunits that are critical for killing primary human neutrophils. Remarkably, leukocidins lacking these glycine-rich motifs exhibit dominant-negative inhibitory effects toward their wild-type toxin counterparts as well as other leukocidins. Biochemical and cellular assays revealed that these dominant-negative toxins work by forming mixed complexes that are impaired in pore formation. The dominant-negative leukocidins inhibited S. aureus cytotoxicity toward primary human neutrophils, protected mice from lethal challenge by wild-type leukocidin, and reduced bacterial burden in a murine model of bloodstream infection. Thus, we describe the first example of staphylococcal bi-component dominant-negative toxins and their potential as novel therapeutics to combat S. aureus infection.

Indexed as

MutationAnimalsCytotoxinsFemaleGlycineHumansLeukocidinsMiceNeutrophilsPhagocytesProtein DomainsProtein MultimerizationStaphylococcal InfectionsStaphylococcus aureusVirulenceCytotoxinsGlycineLeukocidinsbi‐componentdominant‐negativeleukocidinpore‐forming toxinStaphylococcus aureus

Identifiers

PMID26882549
PMCPMC4772982
OpenAlexW2263759014

What OpenQuestion holds

Textmetadata
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.