Journal
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
Volume 53, Issue 5, Pages 582-588Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijantimicag.2019.01.003
Keywords
Burkholderia pseudomallei; Ceftazidime; Resistance; beta-Lactamase; Gene duplication; Amplification
Funding
- University of Florida Preeminence Initiative start-up funds
- CRDF Global Grant [OISE-9531011]
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Ceftazidime (CAZ) is the antibiotic of choice for the treatment of Burkholderia pseudomallei infection (melioidosis). The chromosomally-encoded PenA beta-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 beta-lactamases may be a common CAZ resistance mechanism in B. pseudomallei. (C) 2019 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.
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