Evidence map›Paper›PMID 26151066›Full record

ArticleMolecular therapy. Methods & clinical development2015

Structure-based redesign of lysostaphin yields potent antistaphylococcal enzymes that evade immune cell surveillance.

Kristina Blazanovic, Hongliang Zhao, Yoonjoo Choi, Wen Li, Regina S Salvat, Daniel C Osipovitch, Jennifer Fields, Leonard Moise, Brent L Berwin, Steven N Fiering and 2 more

Abstract read
In one paragraph

Article in Molecular therapy. Methods & clinical development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing 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

27 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Endolysins: targetingFrontiers in microbiology · 2025
    Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Selective Eradication ofAntibiotics (Basel, Switzerland) · 2020
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Hydrogel delivery of lysostaphin eliminates orthopedic implant infection byProceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  19. Article
  20. 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

12 authors.

Kristina BlazanovicThayer School of Engineering, Dartmouth , Hanover, New Hampshire, USA.
Hongliang ZhaoThayer School of Engineering, Dartmouth , Hanover, New Hampshire, USA ; Laboratory of Microorganism Engineering, Beijing Institute of Biotechnology , Beijing, People's Republic of China.
Yoonjoo ChoiDepartment of Computer Science, Dartmouth , Hanover, New Hampshire, USA.
Wen LiThayer School of Engineering, Dartmouth , Hanover, New Hampshire, USA.
Regina S SalvatThayer School of Engineering, Dartmouth , Hanover, New Hampshire, USA.
Daniel C OsipovitchProgram in Experimental and Molecular Medicine, Dartmouth , Hanover, New Hampshire, USA.
Jennifer FieldsDepartment of Microbiology and Immunology, Dartmouth , Hanover, New Hampshire, USA.
Leonard MoiseInstitute for Immunology and Informatics, University of Rhode Island , Providence, Rhode Island, USA.
Brent L BerwinDepartment of Microbiology and Immunology, Dartmouth , Hanover, New Hampshire, USA ; Norris Cotton Cancer Center, Dartmouth , Hanover, New Hampshire, USA.
Steven N FieringDepartment of Microbiology and Immunology, Dartmouth , Hanover, New Hampshire, USA ; Norris Cotton Cancer Center, Dartmouth , Hanover, New Hampshire, USA.
Chris Bailey-KelloggDepartment of Computer Science, Dartmouth , Hanover, New Hampshire, USA.
Karl E GriswoldThayer School of Engineering, Dartmouth , Hanover, New Hampshire, USA ; Norris Cotton Cancer Center, Dartmouth , Hanover, New Hampshire, USA ; Department of Biological Sciences, Dartmouth , Hanover, New Hampshire, USA.

Funding

Translational Engineering in Cancer (TEC)P30CA023108 · NCI · DARTMOUTH COLLEGE · PI Steven D Leach · 1985 to 2026
$91.3M
SYNERGY: The Dartmouth Center for clinical and Translational ScienceUL1TR001086 · NCATS · DARTMOUTH COLLEGE · PI GREEN, ALAN I · 2013 to 2017
$18.3M
TRANSLATIONAL RESEARCH COREP30GM106394 · NIGMS · DARTMOUTH COLLEGE · PI O'TOOLE, GEORGE A. · 2013 to 2017
$6.1M
Center for Molecular, Cellular, and Translational ImmunologyP30GM103415 · NIGMS · DARTMOUTH COLLEGE · PI GREEN, WILLIAM R · 2012 to 2015
$4.7M
Functional Deimmunization of Therapeutic ProteinsR01GM098977 · NIGMS · DARTMOUTH COLLEGE · PI BAILEY-KELLOGG, CHRIS, GRISWOLD, KARL E · 2011 to 2019
$3.4M
Computationally optimized anti-staphylococcal biotherapeuticsR21AI098122 · NIAID · DARTMOUTH COLLEGE · PI BAILEY-KELLOGG, CHRIS, DEGROOT, ANNE SEARLS · 2012 to 2013
$451k
NCATS NIH HHS UL1 TR001086NCI NIH HHS P30 CA023108NIAID NIH HHS R21 AI098122NIGMS NIH HHS P30 GM103415NIGMS NIH HHS P30 GM106394NIGMS NIH HHS R01 GM098977
6 · The paper itself

Abstract

Staphylococcus aureus infections exert a tremendous burden on the health-care system, and the threat of drug-resistant strains continues to grow. The bacteriolytic enzyme lysostaphin is a potent antistaphylococcal agent with proven efficacy against both drug-sensitive and drug-resistant strains; however, the enzyme's own bacterial origins cause undesirable immunogenicity and pose a barrier to clinical translation. Here, we deimmunized lysostaphin using a computationally guided process that optimizes sets of mutations to delete immunogenic T cell epitopes without disrupting protein function. In vitro analyses showed the methods to be both efficient and effective, producing seven different deimmunized designs exhibiting high function and reduced immunogenic potential. Two deimmunized candidates elicited greatly suppressed proliferative responses in splenocytes from humanized mice, while at the same time the variants maintained wild-type efficacy in a staphylococcal pneumonia model. Overall, the deimmunized enzymes represent promising leads in the battle against S. aureus.

Identifiers

PMID26151066
PMCPMC4470366

What OpenQuestion holds

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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.