RRC ID 53684
Author Yosef I, Manor M, Kiro R, Qimron U.
Title Temperate and lytic bacteriophages programmed to sensitize and kill antibiotic-resistant bacteria.
Journal Proc Natl Acad Sci U S A
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.
Volume 112(23)
Pages 7267-72
Published 2015-6-9
DOI 10.1073/pnas.1500107112
PII 1500107112
PMID 26060300
PMC PMC4466736
MeSH Bacteria / genetics Bacteria / virology* Bacteriophages / physiology* Clustered Regularly Interspaced Short Palindromic Repeats Drug Resistance, Bacterial* Lysogeny Plasmids
IF 9.412
Times Cited 154
Resource
Prokaryotes E. coli