Evidence map›Paper›PMID 35642538›Full record

ArticlemSphere2022

Neutralizing Staphylococcus aureus Virulence with AZD6389, a Three mAb Combination, Accelerates Closure of a Diabetic Polymicrobial Wound.

Christine Tkaczyk, Omari Jones-Nelson, Yue Yue Shi, David E Tabor, Lily Cheng, Tianhui Zhang, Bret R Sellman

Open access · goldAbstract read
In one paragraph

Article in mSphere, 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
3.9field-weighted citation impact, top 5% 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, 28 citations in OpenAlex.

  1. Review
  2. Article
  3. Antimicrobial photodynamic therapy withFrontiers in cellular and infection microbiology · 2026
    Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. In vivo mRNA expression of a multi-mechanistic mAb combination protects against Staphylococcus aureus infection.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Article
  9. Review
  10. Review
  11. Review
  12. Article
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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

7 authors at 1 institution in 1 country.

Christine TkaczykEarly Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA.ORCID 0000-0002-3346-8131
Omari Jones-NelsonEarly Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA.
Yue Yue ShiEarly Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA.
David E TaborEarly Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA.
Lily ChengOncology Safety, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Gaithersburg, Maryland, USA.
Tianhui ZhangData Sciences and Quantitative Biology AstraZeneca, Gaithersburg, Maryland, USA.
Bret R SellmanEarly Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA.
AstraZeneca (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Nonhealing diabetic foot ulcers (DFU), a major complication of diabetes, are associated with high morbidity and mortality despite current standard of care. Since Staphylococcus aureus is the most common pathogen isolated from nonhealing and infected DFU, we hypothesized that S. aureus virulence factors would damage tissue, promote immune evasion and alter the microbiome, leading to bacterial persistence and delayed wound healing. In a diabetic mouse polymicrobial wound model with S. aureus, Pseudomonas aeruginosa, and Streptococcus pyogenes, we report a rapid bacterial proliferation, prolonged pro-inflammatory response and large necrotic lesions unclosed for up to 40 days. Treatment with AZD6389, a three-monoclonal antibody combination targeting S. aureus alpha toxin, 4 secreted leukotoxins, and fibrinogen binding cell-surface adhesin clumping factor A resulted in full skin re-epithelization 21 days after inoculation. By neutralizing multiple virulence factors, AZD6389 effectively blocked bacterial agglutination and S. aureus-mediated cell killing, abrogated S. aureus-mediated immune evasion and targeted the bacteria for opsonophagocytic killing. Neutralizing S. aureus virulence not only facilitated S. aureus clearance in lesions, but also reduced S. pyogenes and P. aeruginosa numbers, damaging inflammatory mediators and markers for neutrophil extracellular trap formation 14 days post initiation. Collectively, our data suggest that AZD6389 holds promise as an immunotherapeutic approach against DFU complications.

Indexed as

Diabetes MellitusDiabetic FootStaphylococcal InfectionsAnimalsAntibodies, MonoclonalBacteriaMicePseudomonas aeruginosaQuality of LifeStaphylococcus aureusVirulenceVirulence FactorsAntibodies, MonoclonalVirulence Factorsalpha toxinclumping factor Adiabetic footleukocidinsmonoclonal antibodiespolymicrobial infectionsStaphylococcus aureuswound healing

Identifiers

PMID35642538
PMCPMC9241520
OpenAlexW4281868931

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.