Evidence map›Paper›PMID 31585083›Full record

ArticleCell2019

Engineering Phage Host-Range and Suppressing Bacterial Resistance through Phage Tail Fiber Mutagenesis.

Kevin Yehl, Sébastien Lemire, Andrew C Yang, Hiroki Ando, Mark Mimee, Marcelo Der Torossian Torres, Cesar de la Fuente-Nunez, Timothy K Lu

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 254 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
254citing papers in PubMed, 1 pooled it
–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

254 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Review
  4. Escherichia coli bacteriophage vB_EcoS_MS2 effectively prevents biofilm formation but shows limited activity against mature biofilms.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2026
    Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Bacterial immune systems.Antonie van Leeuwenhoek · 2026
    Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Kevin YehlSynthetic Biology Group, MIT Synthetic Biology Center, The Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA; Research Laboratory of Electronics, MIT, Cambridge, MA 02139, USA.
Sébastien LemireSynthetic Biology Group, MIT Synthetic Biology Center, The Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA; Research Laboratory of Electronics, MIT, Cambridge, MA 02139, USA.
Andrew C YangSynthetic Biology Group, MIT Synthetic Biology Center, The Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
Hiroki AndoSynthetic Biology Group, MIT Synthetic Biology Center, The Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA; Research Laboratory of Electronics, MIT, Cambridge, MA 02139, USA.
Mark MimeeSynthetic Biology Group, MIT Synthetic Biology Center, The Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA; Research Laboratory of Electronics, MIT, Cambridge, MA 02139, USA.
Marcelo Der Torossian TorresSynthetic Biology Group, MIT Synthetic Biology Center, The Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA; Research Laboratory of Electronics, MIT, Cambridge, MA 02139, USA.
Cesar de la Fuente-NunezSynthetic Biology Group, MIT Synthetic Biology Center, The Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA; Research Laboratory of Electronics, MIT, Cambridge, MA 02139, USA.
Timothy K LuSynthetic Biology Group, MIT Synthetic Biology Center, The Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA; Research Laboratory of Electronics, MIT, Cambridge, MA 02139, USA; Department of Electrical Engineering and Computer Science, MIT, Cambridge, MA 02139, USA; Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139, USA; Department of Biological Engineering, MIT, Cambridge, MA 02129, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: timlu@mit.edu.

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI MATTHEW G. VANDER HEIDEN · 1985 to 2026
$93.9M
MIT Center for Integrative Synthetic BiologyP50GM098792 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI WEISS, RON · 2013 to 2017
$11.0M
Mucin Glycans in the Regulation of Microbial VirulenceR01EB017755 · NIBIB · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI RIBBECK, KATHARINA · 2013 to 2022
$3.6M
High-Throughput Nanoscale Approaches to Studying and Inhibiting Amyloid ToxicityDP2OD008435 · OD · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI LU, TIMOTHY · 2011 to 2011
$2.4M
Engineering “Phagebody” Antimicrobials for Carbapenem-Resistant EnterobacteriaceaeR33AI121669 · NIAID · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI LU, TIMOTHY · 2018 to 2020
$1.3M
Engineering “Phagebody” Antimicrobials for Carbapenem-Resistant EnterobacteriaceaeR21AI121669 · NIAID · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI LU, TIMOTHY · 2016 to 2017
$403k
NCI NIH HHS P30 CA014051NIAID NIH HHS R21 AI121669NIAID NIH HHS R33 AI121669NIBIB NIH HHS R01 EB017755NIGMS NIH HHS P50 GM098792NIH HHS DP2 OD008435
6 · The paper itself

Abstract

The rapid emergence of antibiotic-resistant infections is prompting increased interest in phage-based antimicrobials. However, acquisition of resistance by bacteria is a major issue in the successful development of phage therapies. Through natural evolution and structural modeling, we identified host-range-determining regions (HRDRs) in the T3 phage tail fiber protein and developed a high-throughput strategy to genetically engineer these regions through site-directed mutagenesis. Inspired by antibody specificity engineering, this approach generates deep functional diversity while minimizing disruptions to the overall tail fiber structure, resulting in synthetic "phagebodies." We showed that mutating HRDRs yields phagebodies with altered host-ranges, and select phagebodies enable long-term suppression of bacterial growth in vitro, by preventing resistance appearance, and are functional in vivo using a murine model. We anticipate that this approach may facilitate the creation of next-generation antimicrobials that slow resistance development and could be extended to other viral scaffolds for a broad range of applications.

Indexed as

AnimalsBacteriophage T3Drug Resistance, BacterialEscherichia coliEscherichia coli InfectionsHost SpecificityMiceMutagenesis, Site-DirectedPhage TherapySkin Diseases, BacterialViral Tail ProteinsViral Tail Proteinsantibodyantimicrobialbacteriophageevolutionhost-rangephageresistancesynthetic biologytail fibervirus

Identifiers

PMID31585083
PMCPMC6924272

What OpenQuestion holds

Textmetadata
LicenceTDM
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.