title: AcrAB multidrug efflux pump is associated with reduced levels of susceptibility to tigecycline (GAR-936) in Proteus mirabilis.
abstract: Tigecycline has good broad-spectrum activity against many gram-positive and gram-negative pathogens with the notable exception of the PROTEEAE: A study was performed to identify the mechanism responsible for the reduced susceptibility to tigecycline in Proteus mirabilis. Two independent transposon insertion mutants of P. mirabilis that had 16-fold-increased susceptibility to tigecycline were mapped to the acrB gene homolog of the Escherichia coli AcrRAB efflux system. Wild-type levels of decreased susceptibility to tigecycline were restored to the insertion mutants by complementation with a clone containing a PCR-derived fragment from the parental wild-type acrRAB efflux gene cluster. The AcrAB transport system appears to be associated with the intrinsic reduced susceptibility to tigecycline in P. mirabilis.
authors.affiliation: Wyeth Research, Pearl River, New York, USA. visallm@wyeth.com
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Visalli
authors.forename: Ellen
authors.initials: E
authors.lastname: Murphy
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Projan
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Bradford
mesh_terms: D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology; D004251:DNA Transposable Elements / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology*; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011513:Proteus mirabilis / Q000187:drug effects* / Q000235:genetics; D000078304:Tigecycline
chemical_list: D002352:Carrier Proteins; D004251:DNA Transposable Elements; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D008911:Minocycline; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000078304:Tigecycline; C083496:AcrB protein, E coli