Evidence map›Paper›PMID 32694655›Full record

ArticleScientific reports2020

Exploiting phage receptor binding proteins to enable endolysins to kill Gram-negative bacteria.

Athina Zampara, Martine C Holst Sørensen, Dennis Grimon, Fabio Antenucci, Amira Ruslanovna Vitt, Valeria Bortolaia, Yves Briers, Lone Brøndsted

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
9.1field-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

58 citing papers in PubMed, 108 citations in OpenAlex.

  1. Prophage-Derived Molecules as Anti-Antibiotics (Basel, Switzerland) · 2026
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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

8 authors at 3 institutions in 2 countries.

Athina ZamparaDepartment of Veterinary and Animal Sciences, University of Copenhagen, Stigbøjlen 4, 1870, Frederiksberg C, Denmark.
Martine C Holst SørensenDepartment of Veterinary and Animal Sciences, University of Copenhagen, Stigbøjlen 4, 1870, Frederiksberg C, Denmark.
Dennis GrimonDepartment of Biotechnology, Ghent University, Valentin Vaerwyckweg 1, 9000, Gent, Belgium.
Fabio AntenucciDepartment of Veterinary and Animal Sciences, University of Copenhagen, Stigbøjlen 4, 1870, Frederiksberg C, Denmark.
Amira Ruslanovna VittDepartment of Veterinary and Animal Sciences, University of Copenhagen, Stigbøjlen 4, 1870, Frederiksberg C, Denmark.
Valeria BortolaiaNational Food Institute, Technical University of Denmark, WHO Collaborating Center for Antimicrobial Resistance in Food Borne Pathogens and Genomics and European Union Reference Laboratory for Antimicrobial Resistance, Kemitorvet 204, 2800, Kongens Lyngby, Denmark.
Yves BriersDepartment of Biotechnology, Ghent University, Valentin Vaerwyckweg 1, 9000, Gent, Belgium.
Lone BrøndstedDepartment of Veterinary and Animal Sciences, University of Copenhagen, Stigbøjlen 4, 1870, Frederiksberg C, Denmark. lobr@sund.ku.dk.
University of Copenhagen · DKGhent University · BETechnical University of Denmark · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Bacteriophage-encoded endolysins degrading the bacterial peptidoglycan are promising antibacterials for combating antibiotic-resistant bacteria. However, endolysins have limited use against Gram-negative bacteria, since the outer membrane prevents access to the peptidoglycan. Here, we present Innolysins, an innovative concept for engineering endolysins to exert antibacterial activity against Gram-negative bacteria. Innolysins combine the enzymatic activity of endolysins with the binding capacity of phage receptor binding proteins (RBPs). As proof-of-concept, we constructed 12 Innolysins by fusing phage T5 endolysin and RBP Pb5 in different configurations. One of these, Innolysin Ec6 displayed antibacterial activity against Escherichia coli only in the presence of Pb5 receptor FhuA, leading to 1.22 ± 0.12 log reduction in cell counts. Accordingly, other bacterial species carrying FhuA homologs such as Shigella sonnei and Pseudomonas aeruginosa were sensitive to Innolysin Ec6. To enhance the antibacterial activity, we further constructed 228 novel Innolysins by fusing 23 endolysins with Pb5. High-throughput screening allowed to select Innolysin Ec21 as the best antibacterial candidate, leading to 2.20 ± 0.09 log reduction in E. coli counts. Interestingly, Innolysin Ec21 also displayed bactericidal activity against E. coli resistant to third-generation cephalosporins, reaching a 3.31 ± 0.53 log reduction in cell counts. Overall, the Innolysin approach expands previous endolysin-engineering strategies, allowing customization of endolysins by exploiting phage RBPs to specifically target Gram-negative bacteria.

Indexed as

Amino Acid SequenceBacterial Outer Membrane ProteinsBacteriophagesDisintegrinsEndopeptidasesEscherichia coliEscherichia coli ProteinsGram-Negative BacteriaViral ProteinsBacterial Outer Membrane ProteinsDisintegrinsendolysinEndopeptidasesEscherichia coli ProteinsFhuA protein, E coliViral Proteins

Identifiers

PMID32694655
PMCPMC7374709
OpenAlexW3044356666

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.