Temperate and lytic bacteriophages programmed to sensitize and kill antibiotic-resistant bacteria

Ido Yosef, Miriam Manor, Ruth Kiro, Udi Qimron*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

339 Scopus citations

Abstract

The increasing threat of pathogen resistance to antibiotics requires the development of novel antimicrobial strategies. Here we present a proof of concept for a genetic strategy that aims to sensitize bacteria to antibiotics and selectively kill antibiotic-resistant bacteria. We use temperate phages to deliver a functional clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPRassociated (Cas) system into the genome of antibiotic-resistant bacteria. The delivered CRISPR-Cas system destroys both antibiotic resistance-conferring plasmids and genetically modified lytic phages. This linkage between antibiotic sensitization and protection from lytic phages is a key feature of the strategy. It allows programming of lytic phages to kill only antibiotic-resistant bacteria while protecting antibiotic-sensitized bacteria. Phages designed according to this strategy may be used on hospital surfaces and hand sanitizers to facilitate replacement of antibioticresistant pathogens with sensitive ones.

Original languageEnglish
Pages (from-to)7267-7272
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number23
DOIs
StatePublished - 9 Jun 2015

Funding

FundersFunder number
European Research Council336079
Israel Science Foundation268/14

    Keywords

    • CRISPR-Cas
    • Ex vivo treatment
    • Lysogenization
    • Positive selection

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