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Antimicrobial Agents and Chemotherapy, July 2003, p. 2082-2087, Vol. 47, No. 7
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.7.2082-2087.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Burkholderia pseudomallei Class A ß-Lactamase Mutations That Confer Selective Resistance against Ceftazidime or Clavulanic Acid Inhibition

Department of Microbiology, Mahidol University, Bangkok 10700, Thailand,¹ Department of Microbiology and Infectious Diseases, University of Calgary Health Sciences Centre, Calgary, Alberta, Canada T2N 4N12²

Received 25 October 2002/ Returned for modification 24 January 2003/ Accepted 29 March 2003

Burkholderia pseudomallei, the causative agent of melioidosis, is inherently resistant to a variety of antibiotics including aminoglycosides, macrolides, polymyxins, and ß-lactam antibiotics. Despite resistance to many ß-lactams, ceftazidime and ß-lactamase inhibitor-ß-lactam combinations are commonly used for treatment of melioidosis. Here, we examine the enzyme kinetics of ß-lactamase isolated from mutants resistant to ceftazidime and clavulanic acid inhibition and describe specific mutations within conserved motifs of the ß-lactamase enzyme which account for these resistance patterns. Sequence analysis of regions flanking the B. pseudomallei penA gene revealed a putative regulator gene located downstream of penA. We have cloned and sequenced the penA gene from B. mallei and found it to be identical to penA from B. pseudomallei.

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