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Antimicrobial Agents and Chemotherapy, September 2009, p. 3628-3634, Vol. 53, No. 9
0066-4804/09/$08.00+0     doi:10.1128/AAC.00284-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Resistance to Colistin in Acinetobacter baumannii Associated with Mutations in the PmrAB Two-Component System{triangledown}

Mark D. Adams,1* Gabrielle C. Nickel,1 Saralee Bajaksouzian,2,4 Heather Lavender,1 A. Rekha Murthy,4 Michael R. Jacobs,2,5 and Robert A. Bonomo3,6

Departments of Genetics,1 Pathology,2 Pharmacology and Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, Ohio,3 Department of Hospital Epidemiology, Division of Infectious Diseases, Cedars-Sinai Medical Center, Los Angeles, California,4 Department of Pathology, University Hospitals Case Medical Center, Cleveland, Ohio,5 Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio6

Received 2 March 2009/ Returned for modification 1 May 2009/ Accepted 9 June 2009

The mechanism of colistin resistance (Colr) in Acinetobacter baumannii was studied by selecting in vitro Colr 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 Colr clinical isolate. A colistin-susceptible revertant of one Colr 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 Colr mutants, but not at a low pH, suggesting that additional regulatory factors remain to be discovered.

* Corresponding author. Mailing address: Department of Genetics, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106-4955. Phone: (216) 368-2791. Fax: (216) 368-3432. E-mail: mda13{at}case.edu

{triangledown} Published ahead of print on 15 June 2009.

Antimicrobial Agents and Chemotherapy, September 2009, p. 3628-3634, Vol. 53, No. 9
0066-4804/09/$08.00+0     doi:10.1128/AAC.00284-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Nemec, A., Dijkshoorn, L. (2010). Variations in colistin susceptibility among different species of the genus Acinetobacter. J Antimicrob Chemother 65: 367-369 [Full Text]  


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