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Ceftazidime (CAZ) is the antibiotic of choice for the treatment of Burkholderia pseudomallei infection (melioidosis). The chromosomally-encoded PenA β-lactamase possesses weak cephalosporinase activity. The wild-type penA gene confers clinically significant CAZ resistance only when overexpressed due to a promoter mutation, transcriptional antitermination or by gene duplication and amplification (GDA). Here we characterise a reversible 33-kb GDA event involving wild-type penA in a CAZ-resistant B. pseudomallei clinical isolate from Thailand. We show that duplication arises from exchanges between short (<10 bp) chromosomal sequences, which in this example consist of 4-bp repeats flanked by 3-bp inverted repeats. GDA involving β-lactamases may be a common CAZ resistance mechanism in B. pseudomallei.

Original publication

DOI

10.1016/j.ijantimicag.2019.01.003

Type

Journal article

Journal

International journal of antimicrobial agents

Publication Date

05/2019

Volume

53

Pages

582 - 588

Addresses

Department of Molecular Genetics and Microbiology, College of Medicine, Emerging Pathogens Institute, Institute for Therapeutic Innovation, University of Florida, Gainesville, FL, USA.