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Proc Natl Acad Sci U S A. 2015 Jun 9;112(23):7267-72. doi: 10.1073/pnas.1500107112. Epub 2015 May 18.

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

Author information

1
Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
2
Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel ehudq@post.tau.ac.il.

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)-CRISPR-associated (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 antibiotic-resistant pathogens with sensitive ones.

KEYWORDS:

CRISPR-Cas; ex vivo treatment; lysogenization; positive selection

PMID:
26060300
PMCID:
PMC4466736
DOI:
10.1073/pnas.1500107112
[Indexed for MEDLINE]
Free PMC Article

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