Navigation auf zora.uzh.ch

Search ZORA

ZORA (Zurich Open Repository and Archive)

Reprogramming Bacteriophage Host Range through Structure-Guided Design of Chimeric Receptor Binding Proteins

Dunne, Matthew; Rupf, Beatrice; Tala, Marc; Qabrati, Xhem; Ernst, Patrick; Shen, Yang; Sumrall, Eric; Heeb, Laura; Plückthun, Andreas; Loessner, Martin J; Kilcher, Samuel (2019). Reprogramming Bacteriophage Host Range through Structure-Guided Design of Chimeric Receptor Binding Proteins. Cell Reports, 29(5):1336-1350.e4.

Abstract

Bacteriophages provide excellent tools for diagnostics, remediation, and targeted microbiome manipulation, yet isolating viruses with suitable host specificity remains challenging. Using Listeria phage PSA, we present a synthetic biology blueprint for host-range engineering through targeted modification of serovar-specific receptor binding proteins (RBPs). We identify Gp15 as the PSA RBP and construct a synthetic phage library featuring sequence-randomized RBPs, from which host range mutants are isolated and subsequently integrated into a synthetic, polyvalent phage with extended host range. To enable rational design of chimeric RBPs, we determine the crystal structure of the Gp15 receptor-binding carboxyl terminus at 1.7-Å resolution and employ bioinformatics to identify compatible, prophage-encoded RBPs targeting different Listeria serovars. Structure-guided design enables exchange of heterologous RBP head, neck, or shoulder domains to generate chimeric phages with predictable and extended host ranges. These strategies will facilitate the development of phage biologics based on standardized virus scaffolds with tunable host specificities.

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Department of Biochemistry
07 Faculty of Science > Department of Biochemistry
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Life Sciences > General Biochemistry, Genetics and Molecular Biology
Language:English
Date:29 October 2019
Deposited On:31 Jan 2020 15:15
Last Modified:22 Oct 2024 01:41
Publisher:Cell Press (Elsevier)
ISSN:2211-1247
OA Status:Gold
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.celrep.2019.09.062
PubMed ID:31665644
Download PDF  'Reprogramming Bacteriophage Host Range through Structure-Guided Design of Chimeric Receptor Binding Proteins'.
Preview
  • Content: Published Version
  • Licence: Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

Metadata Export

Statistics

Citations

Dimensions.ai Metrics
122 citations in Web of Science®
127 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

48 downloads since deposited on 31 Jan 2020
7 downloads since 12 months
Detailed statistics

Authors, Affiliations, Collaborations

Similar Publications