Resistance to colistin in Acinetobacter baumannii associated with mutations in the PmrAB two-component system.
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.
Adams
Mark D
MD
Department of Genetics, Case Western Reserve University, Cleveland, OH 44106-4955, USA. mda13@case.edu
Nickel
Gabrielle C
GC
Bajaksouzian
Saralee
S
Lavender
Heather
H
Murthy
A Rekha
AR
Jacobs
Michael R
MR
Bonomo
Robert A
RA
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
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C409039:PmrB protein, bacteria; D014157:Transcription Factors; C081902:pmrA protein, Bacteria; D003091:Colistin