Evidence map›Paper›PMID 22679291›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2012

Structural engineering of a phage lysin that targets gram-negative pathogens.

Petra Lukacik, Travis J Barnard, Paul W Keller, Kaveri S Chaturvedi, Nadir Seddiki, James W Fairman, Nicholas Noinaj, Tara L Kirby, Jeffrey P Henderson, Alasdair C Steven and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed
11.8field-weighted citation impact, top 1% 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

75 citing papers in PubMed, 154 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Retracing the path of evolution: polymorphisms ofEmerging microbes & infections · 2025
    Article
  5. Review
  6. [Phage endolysins-a novel class of antibacterial agents with a wide range of applications].Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz · 2025
    Review
  7. Review
  8. Article
  9. Article
  10. Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. Article
  18. Siderophores as tools and treatments.npj antimicrobials and resistance · 2024
    Review
  19. Article
  20. Review

15 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 1 country.

Petra LukacikLaboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Travis J Barnard
Paul W Keller
Kaveri S Chaturvedi
Nadir Seddiki
James W Fairman
Nicholas Noinaj
Tara L Kirby
Jeffrey P Henderson
Alasdair C Steven
B Joseph Hinnebusch
Susan K Buchanan
National Institutes of Health · USNational Institute of Diabetes and Digestive and Kidney Diseases · USWashington University in St. Louis · USNational Institute of Arthritis and Musculoskeletal and Skin Diseases · US

Funding

Structural characterization of outer membrane proteins from Yersinia pestisZIADK011011 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI BUCHANAN, SUSAN · 2009 to 2025
$19.1M
pan-Genome of E.coli in the bladder and gut of women with recurrent UTIP50DK064540 · NIDDK · WASHINGTON UNIVERSITY · PI HULTGREN, SCOTT J. · 2002 to 2017
$17.9M
Animal Models to Study Plague Infection and ImmunityZIAAI000919 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI HINNEBUSCH, B J · 2009 to 2023
$8.3M
INTERDISCIPLINARY RESEARCH CAREERS IN WOMEN'S HEALTHK12HD001459 · NICHD · WASHINGTON UNIVERSITY · PI SEMENKOVICH, CLAY F. · 2000 to 2014
$6.9M
Structural Biology of Macromolecular ComplexesZIAAR027015 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI STEVEN, ALASDAIR C. · 2009 to 2018
$6.5M
Intramural NIH HHSNICHD NIH HHS K12 HD001459NICHD NIH HHS K12 HD001459-09NIDDK NIH HHS P50 DK064540
6 · The paper itself

Abstract

Bacterial pathogens are becoming increasingly resistant to antibiotics. As an alternative therapeutic strategy, phage therapy reagents containing purified viral lysins have been developed against gram-positive organisms but not against gram-negative organisms due to the inability of these types of drugs to cross the bacterial outer membrane. We solved the crystal structures of a Yersinia pestis outer membrane transporter called FyuA and a bacterial toxin called pesticin that targets this transporter. FyuA is a β-barrel membrane protein belonging to the family of TonB dependent transporters, whereas pesticin is a soluble protein with two domains, one that binds to FyuA and another that is structurally similar to phage T4 lysozyme. The structure of pesticin allowed us to design a phage therapy reagent comprised of the FyuA binding domain of pesticin fused to the N-terminus of T4 lysozyme. This hybrid toxin kills specific Yersinia and pathogenic E. coli strains and, importantly, can evade the pesticin immunity protein (Pim) giving it a distinct advantage over pesticin. Furthermore, because FyuA is required for virulence and is more common in pathogenic bacteria, the hybrid toxin also has the advantage of targeting primarily disease-causing bacteria rather than indiscriminately eliminating natural gut flora.

Indexed as

Bacterial ProteinsBacteriocinsBacteriophagesCell MembraneCryoelectron MicroscopyGram-Negative BacteriaModels, MolecularMucoproteinsProtein ConformationProtein EngineeringProtein TransportReceptors, Cell SurfaceBacterial ProteinsBacteriocinsFyuA protein, Yersinialysin, gastropodaMucoproteinsPesticinReceptors, Cell Surface

Identifiers

PMID22679291
PMCPMC3382549
OpenAlexW2011957174

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.