Contracting the Host Range of Bacteriophage T7 Using a Continuous Evolution System

Tzvi Holtzman*, Ram Nechooshtan, Ido Yosef, Udi Qimron

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

Abstract

Bacteriophage T7 is an intracellular virus that recognizes its host via tail and tail fiber proteins known as receptor-binding proteins (RBPs). The RBPs attach to a specific lipopolysaccharide (LPS) displayed on the host. While there are various reports of phage host range expansion resulting from mutations in the RBP encoding genes, there is little evidence for contraction of host range. Notably, most experimental systems have not monitored changes in host range in the presence of several hosts simultaneously. Here, we use a continuous evolution system to show that T7 phages grown in the presence of five restrictive strains and one permissive host, each with a different LPS, gradually cease to recognize the restrictive strains. Remarkably, this result was obtained in experiments with six different permissive hosts. The altered specificity is due to mutations in the RBPs as determined by gene sequencing. The results of using this system demonstrate a major role for RBPs in restricting the range of futile infections, and this process can be harnessed to reduce the host range in applications such as recognition and elimination of a specific bacterial serotype by bacteriophages.

Original languageEnglish
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Pages85-100
Number of pages16
DOIs
StatePublished - 2024

Publication series

NameMethods in Molecular Biology
Volume2793
ISSN (Print)1064-3745
ISSN (Electronic)1940-6029

Funding

FundersFunder number
European Research Council
Horizon 2020818878
Horizon 2020

    Keywords

    • Aseptic techniquesAseptic techniques
    • Continuous evolution systemContinuous evolution system
    • Continuous fermentation
    • Permissive hostPermissive host
    • Restrictive strainRestrictive strains
    • Specialist phage

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