title: Silencing of antibiotic resistance in E. coli with engineered phage bearing small regulatory RNAs.
abstract: In response to emergent antibiotic resistance, new strategies are needed to enhance the effectiveness of existing antibiotics. Here, we describe a phagemid-delivered, RNA-mediated system capable of directly knocking down antibiotic resistance phenotypes. Small regulatory RNAs (sRNAs) were designed to specifically inhibit translation of chloramphenicol acetyltransferase and kanamycin phosphotransferase. Nonlytic phagemids coding for sRNA expression were able to infect and restore chloramphenicol and kanamycin sensitivity to populations of otherwise resistant E. coli. This modular system could easily be extended to other bacteria with resistance profiles that depend on specific transcripts.
authors.affiliation: 2013 Paris Bettencourt iGEM team, 75014 Paris, France.
authors.forename: Vincent K
authors.initials: VK
authors.lastname: Libis
authors.forename: Aude G
authors.initials: AG
authors.lastname: Bernheim
authors.forename: Clovis
authors.initials: C
authors.lastname: Basier
authors.forename: Sebastián
authors.initials: S
authors.lastname: Jaramillo-Riveri
authors.forename: Matthew
authors.initials: M
authors.lastname: Deyell
authors.forename: Idonnya
authors.initials: I
authors.lastname: Aghoghogbe
authors.forename: Iva
authors.initials: I
authors.lastname: Atanaskovic
authors.forename: Amel Camélia
authors.initials: AC
authors.lastname: Bencherif
authors.forename: Marguerite
authors.initials: M
authors.lastname: Benony
authors.forename: Nicolas
authors.initials: N
authors.lastname: Koutsoubelis
authors.forename: Anne C
authors.initials: AC
authors.lastname: Löchner
authors.forename: Zoran S
authors.initials: ZS
authors.lastname: Marinkovic
authors.forename: Sarah
authors.initials: S
authors.lastname: Zahra
authors.forename: Yonatan
authors.initials: Y
authors.lastname: Zegman
authors.forename: Ariel B
authors.initials: AB
authors.lastname: Lindner
authors.forename: Edwin H
authors.initials: EH
authors.lastname: Wintermute
mesh_terms: D001435:Bacteriophages / Q000235:genetics*; D004352:Drug Resistance, Microbial / Q000187:drug effects / Q000235:genetics*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D020868:Gene Silencing; D005818:Genetic Engineering; D012367:RNA, Viral / Q000235:genetics / Q000494:pharmacology
chemical_list: D012367:RNA, Viral