title: Resistance to colistin in Acinetobacter baumannii associated with mutations in the PmrAB two-component system.
abstract: The mechanism of colistin resistance (Col(r)) in Acinetobacter baumannii was studied by selecting in vitro Col(r) derivatives of the multidrug-resistant A. baumannii isolate AB0057 and the drug-susceptible strain ATCC 17978, using escalating concentrations of colistin in liquid culture. DNA sequencing identified mutations in genes encoding the two-component system proteins PmrA and/or PmrB in each strain and in a Col(r) clinical isolate. A colistin-susceptible revertant of one Col(r) mutant strain, obtained following serial passage in the absence of colistin selection, carried a partial deletion of pmrB. Growth of AB0057 and ATCC 17978 at pH 5.5 increased the colistin MIC and conferred protection from killing by colistin in a 1-hour survival assay. Growth in ferric chloride [Fe(III)] conferred a small protective effect. Expression of pmrA was increased in Col(r) mutants, but not at a low pH, suggesting that additional regulatory factors remain to be discovered.
authors.affiliation: Department of Genetics, Case Western Reserve University, Cleveland, OH 44106-4955, USA. mda13@case.edu
authors.forename: Mark D
authors.initials: MD
authors.lastname: Adams
authors.forename: Gabrielle C
authors.initials: GC
authors.lastname: Nickel
authors.forename: Saralee
authors.initials: S
authors.lastname: Bajaksouzian
authors.forename: Heather
authors.initials: H
authors.lastname: Lavender
authors.forename: A Rekha
authors.initials: AR
authors.lastname: Murthy
authors.forename: Michael R
authors.initials: MR
authors.lastname: Jacobs
authors.forename: Robert A
authors.initials: RA
authors.lastname: Bonomo
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000235:genetics*; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics* / Q000502:physiology; D003091:Colistin / Q000494:pharmacology*; D004252:DNA Mutational Analysis; D024881:Drug Resistance, Bacterial / Q000235:genetics; D016680:Genome, Bacterial / Q000235:genetics; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C409039:PmrB protein, bacteria; D014157:Transcription Factors; C081902:pmrA protein, Bacteria; D003091:Colistin