The patent covers methods for inhibiting a new gene locus, acrAB, which is associated with drug resistance and part of Paratek's "MAR" (Multiple Antibiotic Resistance) program.
The acrAB gene operates within the complex MAR system.
In the January ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Levy and his colleagues show that when they genetically engineer fluoroquinolone-resistant Escherichia coli to lack a normal efflux pump known as AcrAB
, the bacteria become susceptible to the antibiotic again.
The high-level resistance to ethidium bromide and the increased susceptibility of the strains to ciprofloxacin in the presence of Phe-Arg-[beta]-naphthylamide were strongly suggestive of an activated drug efflux system, such as AcrAB
, the substrates of which also include cephalosporins with lipophilic side chains (2,14).
Selection of multiple antibiotic-resistant (mar) mutants of Escherichia coli by using the disinfectant pine oil: roles of the mar and acrAB