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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.

Keywords

Humans, Burkholderia pseudomallei, Melioidosis, Ceftazidime, beta-Lactamases, DNA, Bacterial, Anti-Bacterial Agents, Drug Resistance, Bacterial, Gene Amplification, Gene Duplication, Thailand