PMID: 9420041Jan 7, 1998Paper

Inhibition of the multiple antibiotic resistance (mar) operon in Escherichia coli by antisense DNA analogs

Antimicrobial Agents and Chemotherapy
David G WhiteS B Levy

Abstract

The multiple antibiotic resistance operon (marORAB) in Escherichia coli controls intrinsic susceptibility and resistance to multiple, structurally different antibiotics and other noxious agents. A plasmid construct with marA cloned in the antisense direction reduced LacZ expression from a constitutively expressed marA::lacZ translational fusion and inhibited the induced expression of LacZ in cells bearing the wild-type repressed fusion. The marA antisense construction also decreased the multiple antibiotic resistance of a Mar mutant. Two antisense phosphorothioate oligonucleotides, one targeted to marO and the other targeted to marA of the mar operon, introduced by heat shock or electroporation reduced LacZ expression in the strain having the marA::lacZ fusion. One antisense oligonucleotide, tested against a Mar mutant of E. coli ML308-225, increased the bactericidal activity of norfloxacin. These studies demonstrate the efficacy of exogenously delivered antisense oligonucleotides targeted to the marRAB operon in inhibiting expression of this chromosomal regulatory locus.

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Citations

Aug 23, 2006·Microbial Drug Resistance : MDR : Mechanisms, Epidemiology, and Disease·Siamak P YazdankhahHilde Kruse
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Sep 14, 2010·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Maria S Ramirez, Marcelo E Tolmasky

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