期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 112, 期 23, 页码 7267-7272出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1500107112
关键词
CRISPR-Cas; positive selection; lysogenization; ex vivo treatment
资金
- European Research Council Grant [336079]
- Marie Curie International Reintegration Grant [GA-2010-266717]
- Israeli Ministry of Health Grant [9988-3]
- Israel Science Foundation Grant [268/14]
- European Research Council (ERC) [336079] Funding Source: European Research Council (ERC)
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.
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